@article {10785, title = {Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.}, journal = {Nat Genet}, volume = {50}, year = {2018}, month = {2018 Oct}, pages = {1412-1425}, abstract = {

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

}, issn = {1546-1718}, doi = {10.1038/s41588-018-0205-x}, author = {Evangelou, Evangelos and Warren, Helen R and Mosen-Ansorena, David and Mifsud, Borbala and Pazoki, Raha and Gao, He and Ntritsos, Georgios and Dimou, Niki and Cabrera, Claudia P and Karaman, Ibrahim and Ng, Fu Liang and Evangelou, Marina and Witkowska, Katarzyna and Tzanis, Evan and Hellwege, Jacklyn N and Giri, Ayush and Velez Edwards, Digna R and Sun, Yan V and Cho, Kelly and Gaziano, J Michael and Wilson, Peter W F and Tsao, Philip S and Kovesdy, Csaba P and Esko, T{\~o}nu and M{\"a}gi, Reedik and Milani, Lili and Almgren, Peter and Boutin, Thibaud and Debette, St{\'e}phanie and Ding, Jun and Giulianini, Franco and Holliday, Elizabeth G and Jackson, Anne U and Li-Gao, Ruifang and Lin, Wei-Yu and Luan, Jian{\textquoteright}an and Mangino, Massimo and Oldmeadow, Christopher and Prins, Bram Peter and Qian, Yong and Sargurupremraj, Muralidharan and Shah, Nabi and Surendran, Praveen and Th{\'e}riault, S{\'e}bastien and Verweij, Niek and Willems, Sara M and Zhao, Jing-Hua and Amouyel, Philippe and Connell, John and de Mutsert, Ren{\'e}e and Doney, Alex S F and Farrall, Martin and Menni, Cristina and Morris, Andrew D and Noordam, Raymond and Par{\'e}, Guillaume and Poulter, Neil R and Shields, Denis C and Stanton, Alice and Thom, Simon and Abecasis, Goncalo and Amin, Najaf and Arking, Dan E and Ayers, Kristin L and Barbieri, Caterina M and Batini, Chiara and Bis, Joshua C and Blake, Tineka and Bochud, Murielle and Boehnke, Michael and Boerwinkle, Eric and Boomsma, Dorret I and Bottinger, Erwin P and Braund, Peter S and Brumat, Marco and Campbell, Archie and Campbell, Harry and Chakravarti, Aravinda and Chambers, John C and Chauhan, Ganesh and Ciullo, Marina and Cocca, Massimiliano and Collins, Francis and Cordell, Heather J and Davies, Gail and de Borst, Martin H and de Geus, Eco J and Deary, Ian J and Deelen, Joris and del Greco M, Fabiola and Demirkale, Cumhur Yusuf and D{\"o}rr, Marcus and Ehret, Georg B and Elosua, Roberto and Enroth, Stefan and Erzurumluoglu, A Mesut and Ferreira, Teresa and Fr{\r a}nberg, Mattias and Franco, Oscar H and Gandin, Ilaria and Gasparini, Paolo and Giedraitis, Vilmantas and Gieger, Christian and Girotto, Giorgia and Goel, Anuj and Gow, Alan J and Gudnason, Vilmundur and Guo, Xiuqing and Gyllensten, Ulf and Hamsten, Anders and Harris, Tamara B and Harris, Sarah E and Hartman, Catharina A and Havulinna, Aki S and Hicks, Andrew A and Hofer, Edith and Hofman, Albert and Hottenga, Jouke-Jan and Huffman, Jennifer E and Hwang, Shih-Jen and Ingelsson, Erik and James, Alan and Jansen, Rick and J{\"a}rvelin, Marjo-Riitta and Joehanes, Roby and Johansson, {\r A}sa and Johnson, Andrew D and Joshi, Peter K and Jousilahti, Pekka and Jukema, J Wouter and Jula, Antti and K{\"a}h{\"o}nen, Mika and Kathiresan, Sekar and Keavney, Bernard D and Khaw, Kay-Tee and Knekt, Paul and Knight, Joanne and Kolcic, Ivana and Kooner, Jaspal S and Koskinen, Seppo and Kristiansson, Kati and Kutalik, Zolt{\'a}n and Laan, Maris and Larson, Marty and Launer, Lenore J and Lehne, Benjamin and Lehtim{\"a}ki, Terho and Liewald, David C M and Lin, Li and Lind, Lars and Lindgren, Cecilia M and Liu, Yongmei and Loos, Ruth J F and Lopez, Lorna M and Lu, Yingchang and Lyytik{\"a}inen, Leo-Pekka and Mahajan, Anubha and Mamasoula, Chrysovalanto and Marrugat, Jaume and Marten, Jonathan and Milaneschi, Yuri and Morgan, Anna and Morris, Andrew P and Morrison, Alanna C and Munson, Peter J and Nalls, Mike A and Nandakumar, Priyanka and Nelson, Christopher P and Niiranen, Teemu and Nolte, Ilja M and Nutile, Teresa and Oldehinkel, Albertine J and Oostra, Ben A and O{\textquoteright}Reilly, Paul F and Org, Elin and Padmanabhan, Sandosh and Palmas, Walter and Palotie, Aarno and Pattie, Alison and Penninx, Brenda W J H and Perola, Markus and Peters, Annette and Polasek, Ozren and Pramstaller, Peter P and Nguyen, Quang Tri and Raitakari, Olli T and Ren, Meixia and Rettig, Rainer and Rice, Kenneth and Ridker, Paul M and Ried, Janina S and Riese, Harri{\"e}tte and Ripatti, Samuli and Robino, Antonietta and Rose, Lynda M and Rotter, Jerome I and Rudan, Igor and Ruggiero, Daniela and Saba, Yasaman and Sala, Cinzia F and Salomaa, Veikko and Samani, Nilesh J and Sarin, Antti-Pekka and Schmidt, Reinhold and Schmidt, Helena and Shrine, Nick and Siscovick, David and Smith, Albert V and Snieder, Harold and S{\~o}ber, Siim and Sorice, Rossella and Starr, John M and Stott, David J and Strachan, David P and Strawbridge, Rona J and Sundstr{\"o}m, Johan and Swertz, Morris A and Taylor, Kent D and Teumer, Alexander and Tobin, Martin D and Tomaszewski, Maciej and Toniolo, Daniela and Traglia, Michela and Trompet, Stella and Tuomilehto, Jaakko and Tzourio, Christophe and Uitterlinden, Andr{\'e} G and Vaez, Ahmad and van der Most, Peter J and van Duijn, Cornelia M and Vergnaud, Anne-Claire and Verwoert, Germaine C and Vitart, Veronique and V{\"o}lker, Uwe and Vollenweider, Peter and Vuckovic, Dragana and Watkins, Hugh and Wild, Sarah H and Willemsen, Gonneke and Wilson, James F and Wright, Alan F and Yao, Jie and Zemunik, Tatijana and Zhang, Weihua and Attia, John R and Butterworth, Adam S and Chasman, Daniel I and Conen, David and Cucca, Francesco and Danesh, John and Hayward, Caroline and Howson, Joanna M M and Laakso, Markku and Lakatta, Edward G and Langenberg, Claudia and Melander, Olle and Mook-Kanamori, Dennis O and Palmer, Colin N A and Risch, Lorenz and Scott, Robert A and Scott, Rodney J and Sever, Peter and Spector, Tim D and van der Harst, Pim and Wareham, Nicholas J and Zeggini, Eleftheria and Levy, Daniel and Munroe, Patricia B and Newton-Cheh, Christopher and Brown, Morris J and Metspalu, Andres and Hung, Adriana M and O{\textquoteright}Donnell, Christopher J and Edwards, Todd L and Psaty, Bruce M and Tzoulaki, Ioanna and Barnes, Michael R and Wain, Louise V and Elliott, Paul and Caulfield, Mark J} } @article {10427, title = {A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.}, journal = {Am J Hum Genet}, volume = {102}, year = {2018}, month = {2018 03 01}, pages = {375-400}, abstract = {

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined \~{}18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5~{\texttimes} 10) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5~{\texttimes} 10). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).

}, keywords = {Blood Pressure, Cohort Studies, Continental Population Groups, Diastole, Epistasis, Genetic, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reproducibility of Results, Smoking, Systole}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2018.01.015}, author = {Sung, Yun J and Winkler, Thomas W and de Las Fuentes, Lisa and Bentley, Amy R and Brown, Michael R and Kraja, Aldi T and Schwander, Karen and Ntalla, Ioanna and Guo, Xiuqing and Franceschini, Nora and Lu, Yingchang and Cheng, Ching-Yu and Sim, Xueling and Vojinovic, Dina and Marten, Jonathan and Musani, Solomon K and Li, Changwei and Feitosa, Mary F and Kilpel{\"a}inen, Tuomas O and Richard, Melissa A and Noordam, Raymond and Aslibekyan, Stella and Aschard, Hugues and Bartz, Traci M and Dorajoo, Rajkumar and Liu, Yongmei and Manning, Alisa K and Rankinen, Tuomo and Smith, Albert Vernon and Tajuddin, Salman M and Tayo, Bamidele O and Warren, Helen R and Zhao, Wei and Zhou, Yanhua and Matoba, Nana and Sofer, Tamar and Alver, Maris and Amini, Marzyeh and Boissel, Mathilde and Chai, Jin Fang and Chen, Xu and Divers, Jasmin and Gandin, Ilaria and Gao, Chuan and Giulianini, Franco and Goel, Anuj and Harris, Sarah E and Hartwig, Fernando Pires and Horimoto, Andrea R V R and Hsu, Fang-Chi and Jackson, Anne U and K{\"a}h{\"o}nen, Mika and Kasturiratne, Anuradhani and Kuhnel, Brigitte and Leander, Karin and Lee, Wen-Jane and Lin, Keng-Hung and {\textquoteright}an Luan, Jian and McKenzie, Colin A and Meian, He and Nelson, Christopher P and Rauramaa, Rainer and Schupf, Nicole and Scott, Robert A and Sheu, Wayne H H and Stan{\v c}{\'a}kov{\'a}, Alena and Takeuchi, Fumihiko and van der Most, Peter J and Varga, Tibor V and Wang, Heming and Wang, Yajuan and Ware, Erin B and Weiss, Stefan and Wen, Wanqing and Yanek, Lisa R and Zhang, Weihua and Zhao, Jing Hua and Afaq, Saima and Alfred, Tamuno and Amin, Najaf and Arking, Dan and Aung, Tin and Barr, R Graham and Bielak, Lawrence F and Boerwinkle, Eric and Bottinger, Erwin P and Braund, Peter S and Brody, Jennifer A and Broeckel, Ulrich and Cabrera, Claudia P and Cade, Brian and Caizheng, Yu and Campbell, Archie and Canouil, Micka{\"e}l and Chakravarti, Aravinda and Chauhan, Ganesh and Christensen, Kaare and Cocca, Massimiliano and Collins, Francis S and Connell, John M and de Mutsert, Ren{\'e}e and de Silva, H Janaka and Debette, St{\'e}phanie and D{\"o}rr, Marcus and Duan, Qing and Eaton, Charles B and Ehret, Georg and Evangelou, Evangelos and Faul, Jessica D and Fisher, Virginia A and Forouhi, Nita G and Franco, Oscar H and Friedlander, Yechiel and Gao, He and Gigante, Bruna and Graff, Misa and Gu, C Charles and Gu, Dongfeng and Gupta, Preeti and Hagenaars, Saskia P and Harris, Tamara B and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hirata, Makoto and Hofman, Albert and Howard, Barbara V and Hunt, Steven and Irvin, Marguerite R and Jia, Yucheng and Joehanes, Roby and Justice, Anne E and Katsuya, Tomohiro and Kaufman, Joel and Kerrison, Nicola D and Khor, Chiea Chuen and Koh, Woon-Puay and Koistinen, Heikki A and Komulainen, Pirjo and Kooperberg, Charles and Krieger, Jose E and Kubo, Michiaki and Kuusisto, Johanna and Langefeld, Carl D and Langenberg, Claudia and Launer, Lenore J and Lehne, Benjamin and Lewis, Cora E and Li, Yize and Lim, Sing Hui and Lin, Shiow and Liu, Ching-Ti and Liu, Jianjun and Liu, Jingmin and Liu, Kiang and Liu, Yeheng and Loh, Marie and Lohman, Kurt K and Long, Jirong and Louie, Tin and M{\"a}gi, Reedik and Mahajan, Anubha and Meitinger, Thomas and Metspalu, Andres and Milani, Lili and Momozawa, Yukihide and Morris, Andrew P and Mosley, Thomas H and Munson, Peter and Murray, Alison D and Nalls, Mike A and Nasri, Ubaydah and Norris, Jill M and North, Kari and Ogunniyi, Adesola and Padmanabhan, Sandosh and Palmas, Walter R and Palmer, Nicholette D and Pankow, James S and Pedersen, Nancy L and Peters, Annette and Peyser, Patricia A and Polasek, Ozren and Raitakari, Olli T and Renstrom, Frida and Rice, Treva K and Ridker, Paul M and Robino, Antonietta and Robinson, Jennifer G and Rose, Lynda M and Rudan, Igor and Sabanayagam, Charumathi and Salako, Babatunde L and Sandow, Kevin and Schmidt, Carsten O and Schreiner, Pamela J and Scott, William R and Seshadri, Sudha and Sever, Peter and Sitlani, Colleen M and Smith, Jennifer A and Snieder, Harold and Starr, John M and Strauch, Konstantin and Tang, Hua and Taylor, Kent D and Teo, Yik Ying and Tham, Yih Chung and Uitterlinden, Andr{\'e} G and Waldenberger, Melanie and Wang, Lihua and Wang, Ya X and Wei, Wen Bin and Williams, Christine and Wilson, Gregory and Wojczynski, Mary K and Yao, Jie and Yuan, Jian-Min and Zonderman, Alan B and Becker, Diane M and Boehnke, Michael and Bowden, Donald W and Chambers, John C and Chen, Yii-Der Ida and de Faire, Ulf and Deary, Ian J and Esko, T{\~o}nu and Farrall, Martin and Forrester, Terrence and Franks, Paul W and Freedman, Barry I and Froguel, Philippe and Gasparini, Paolo and Gieger, Christian and Horta, Bernardo Lessa and Hung, Yi-Jen and Jonas, Jost B and Kato, Norihiro and Kooner, Jaspal S and Laakso, Markku and Lehtim{\"a}ki, Terho and Liang, Kae-Woei and Magnusson, Patrik K E and Newman, Anne B and Oldehinkel, Albertine J and Pereira, Alexandre C and Redline, Susan and Rettig, Rainer and Samani, Nilesh J and Scott, James and Shu, Xiao-Ou and van der Harst, Pim and Wagenknecht, Lynne E and Wareham, Nicholas J and Watkins, Hugh and Weir, David R and Wickremasinghe, Ananda R and Wu, Tangchun and Zheng, Wei and Kamatani, Yoichiro and Laurie, Cathy C and Bouchard, Claude and Cooper, Richard S and Evans, Michele K and Gudnason, Vilmundur and Kardia, Sharon L R and Kritchevsky, Stephen B and Levy, Daniel and O{\textquoteright}Connell, Jeff R and Psaty, Bruce M and van Dam, Rob M and Sims, Mario and Arnett, Donna K and Mook-Kanamori, Dennis O and Kelly, Tanika N and Fox, Ervin R and Hayward, Caroline and Fornage, Myriam and Rotimi, Charles N and Province, Michael A and van Duijn, Cornelia M and Tai, E Shyong and Wong, Tien Yin and Loos, Ruth J F and Reiner, Alex P and Rotter, Jerome I and Zhu, Xiaofeng and Bierut, Laura J and Gauderman, W James and Caulfield, Mark J and Elliott, Paul and Rice, Kenneth and Munroe, Patricia B and Morrison, Alanna C and Cupples, L Adrienne and Rao, Dabeeru C and Chasman, Daniel I} } @article {10823, title = {Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.}, journal = {PLoS One}, volume = {13}, year = {2018}, month = {2018}, pages = {e0198166}, abstract = {

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Alcohol Drinking, Blood Pressure, Cohort Studies, Continental Population Groups, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hypertension, Male, Middle Aged, Pedigree, Polymorphism, Single Nucleotide, Young Adult}, issn = {1932-6203}, doi = {10.1371/journal.pone.0198166}, author = {Feitosa, Mary F and Kraja, Aldi T and Chasman, Daniel I and Sung, Yun J and Winkler, Thomas W and Ntalla, Ioanna and Guo, Xiuqing and Franceschini, Nora and Cheng, Ching-Yu and Sim, Xueling and Vojinovic, Dina and Marten, Jonathan and Musani, Solomon K and Li, Changwei and Bentley, Amy R and Brown, Michael R and Schwander, Karen and Richard, Melissa A and Noordam, Raymond and Aschard, Hugues and Bartz, Traci M and Bielak, Lawrence F and Dorajoo, Rajkumar and Fisher, Virginia and Hartwig, Fernando P and Horimoto, Andrea R V R and Lohman, Kurt K and Manning, Alisa K and Rankinen, Tuomo and Smith, Albert V and Tajuddin, Salman M and Wojczynski, Mary K and Alver, Maris and Boissel, Mathilde and Cai, Qiuyin and Campbell, Archie and Chai, Jin Fang and Chen, Xu and Divers, Jasmin and Gao, Chuan and Goel, Anuj and Hagemeijer, Yanick and Harris, Sarah E and He, Meian and Hsu, Fang-Chi and Jackson, Anne U and K{\"a}h{\"o}nen, Mika and Kasturiratne, Anuradhani and Komulainen, Pirjo and Kuhnel, Brigitte and Laguzzi, Federica and Luan, Jian{\textquoteright}an and Matoba, Nana and Nolte, Ilja M and Padmanabhan, Sandosh and Riaz, Muhammad and Rueedi, Rico and Robino, Antonietta and Said, M Abdullah and Scott, Robert A and Sofer, Tamar and Stan{\v c}{\'a}kov{\'a}, Alena and Takeuchi, Fumihiko and Tayo, Bamidele O and van der Most, Peter J and Varga, Tibor V and Vitart, Veronique and Wang, Yajuan and Ware, Erin B and Warren, Helen R and Weiss, Stefan and Wen, Wanqing and Yanek, Lisa R and Zhang, Weihua and Zhao, Jing Hua and Afaq, Saima and Amin, Najaf and Amini, Marzyeh and Arking, Dan E and Aung, Tin and Boerwinkle, Eric and Borecki, Ingrid and Broeckel, Ulrich and Brown, Morris and Brumat, Marco and Burke, Gregory L and Canouil, Micka{\"e}l and Chakravarti, Aravinda and Charumathi, Sabanayagam and Ida Chen, Yii-Der and Connell, John M and Correa, Adolfo and de Las Fuentes, Lisa and de Mutsert, Ren{\'e}e and de Silva, H Janaka and Deng, Xuan and Ding, Jingzhong and Duan, Qing and Eaton, Charles B and Ehret, Georg and Eppinga, Ruben N and Evangelou, Evangelos and Faul, Jessica D and Felix, Stephan B and Forouhi, Nita G and Forrester, Terrence and Franco, Oscar H and Friedlander, Yechiel and Gandin, Ilaria and Gao, He and Ghanbari, Mohsen and Gigante, Bruna and Gu, C Charles and Gu, Dongfeng and Hagenaars, Saskia P and Hallmans, Goran and Harris, Tamara B and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hirata, Makoto and Howard, Barbara V and Ikram, M Arfan and John, Ulrich and Katsuya, Tomohiro and Khor, Chiea Chuen and Kilpel{\"a}inen, Tuomas O and Koh, Woon-Puay and Krieger, Jose E and Kritchevsky, Stephen B and Kubo, Michiaki and Kuusisto, Johanna and Lakka, Timo A and Langefeld, Carl D and Langenberg, Claudia and Launer, Lenore J and Lehne, Benjamin and Lewis, Cora E and Li, Yize and Lin, Shiow and Liu, Jianjun and Liu, Jingmin and Loh, Marie and Louie, Tin and M{\"a}gi, Reedik and McKenzie, Colin A and Meitinger, Thomas and Metspalu, Andres and Milaneschi, Yuri and Milani, Lili and Mohlke, Karen L and Momozawa, Yukihide and Nalls, Mike A and Nelson, Christopher P and Sotoodehnia, Nona and Norris, Jill M and O{\textquoteright}Connell, Jeff R and Palmer, Nicholette D and Perls, Thomas and Pedersen, Nancy L and Peters, Annette and Peyser, Patricia A and Poulter, Neil and Raffel, Leslie J and Raitakari, Olli T and Roll, Kathryn and Rose, Lynda M and Rosendaal, Frits R and Rotter, Jerome I and Schmidt, Carsten O and Schreiner, Pamela J and Schupf, Nicole and Scott, William R and Sever, Peter S and Shi, Yuan and Sidney, Stephen and Sims, Mario and Sitlani, Colleen M and Smith, Jennifer A and Snieder, Harold and Starr, John M and Strauch, Konstantin and Stringham, Heather M and Tan, Nicholas Y Q and Tang, Hua and Taylor, Kent D and Teo, Yik Ying and Tham, Yih Chung and Turner, Stephen T and Uitterlinden, Andr{\'e} G and Vollenweider, Peter and Waldenberger, Melanie and Wang, Lihua and Wang, Ya Xing and Wei, Wen Bin and Williams, Christine and Yao, Jie and Yu, Caizheng and Yuan, Jian-Min and Zhao, Wei and Zonderman, Alan B and Becker, Diane M and Boehnke, Michael and Bowden, Donald W and Chambers, John C and Deary, Ian J and Esko, T{\~o}nu and Farrall, Martin and Franks, Paul W and Freedman, Barry I and Froguel, Philippe and Gasparini, Paolo and Gieger, Christian and Jonas, Jost Bruno and Kamatani, Yoichiro and Kato, Norihiro and Kooner, Jaspal S and Kutalik, Zolt{\'a}n and Laakso, Markku and Laurie, Cathy C and Leander, Karin and Lehtim{\"a}ki, Terho and Study, Lifelines Cohort and Magnusson, Patrik K E and Oldehinkel, Albertine J and Penninx, Brenda W J H and Polasek, Ozren and Porteous, David J and Rauramaa, Rainer and Samani, Nilesh J and Scott, James and Shu, Xiao-Ou and van der Harst, Pim and Wagenknecht, Lynne E and Wareham, Nicholas J and Watkins, Hugh and Weir, David R and Wickremasinghe, Ananda R and Wu, Tangchun and Zheng, Wei and Bouchard, Claude and Christensen, Kaare and Evans, Michele K and Gudnason, Vilmundur and Horta, Bernardo L and Kardia, Sharon L R and Liu, Yongmei and Pereira, Alexandre C and Psaty, Bruce M and Ridker, Paul M and van Dam, Rob M and Gauderman, W James and Zhu, Xiaofeng and Mook-Kanamori, Dennis O and Fornage, Myriam and Rotimi, Charles N and Cupples, L Adrienne and Kelly, Tanika N and Fox, Ervin R and Hayward, Caroline and van Duijn, Cornelia M and Tai, E Shyong and Wong, Tien Yin and Kooperberg, Charles and Palmas, Walter and Rice, Kenneth and Morrison, Alanna C and Elliott, Paul and Caulfield, Mark J and Munroe, Patricia B and Rao, Dabeeru C and Province, Michael A and Levy, Daniel} } @article {10512, title = {Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.}, journal = {Hypertension}, year = {2017}, month = {2017 Jul 24}, abstract = {

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near , , , , , and , and provide new replication evidence for a further 2 signals in and Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

}, issn = {1524-4563}, doi = {10.1161/HYPERTENSIONAHA.117.09438}, author = {Wain, Louise V and Vaez, Ahmad and Jansen, Rick and Joehanes, Roby and van der Most, Peter J and Erzurumluoglu, A Mesut and O{\textquoteright}Reilly, Paul F and Cabrera, Claudia P and Warren, Helen R and Rose, Lynda M and Verwoert, Germaine C and Hottenga, Jouke-Jan and Strawbridge, Rona J and Esko, T{\~o}nu and Arking, Dan E and Hwang, Shih-Jen and Guo, Xiuqing and Kutalik, Zolt{\'a}n and Trompet, Stella and Shrine, Nick and Teumer, Alexander and Ried, Janina S and Bis, Joshua C and Smith, Albert V and Amin, Najaf and Nolte, Ilja M and Lyytik{\"a}inen, Leo-Pekka and Mahajan, Anubha and Wareham, Nicholas J and Hofer, Edith and Joshi, Peter K and Kristiansson, Kati and Traglia, Michela and Havulinna, Aki S and Goel, Anuj and Nalls, Mike A and S{\~o}ber, Siim and Vuckovic, Dragana and Luan, Jian{\textquoteright}an and del Greco M, Fabiola and Ayers, Kristin L and Marrugat, Jaume and Ruggiero, Daniela and Lopez, Lorna M and Niiranen, Teemu and Enroth, Stefan and Jackson, Anne U and Nelson, Christopher P and Huffman, Jennifer E and Zhang, Weihua and Marten, Jonathan and Gandin, Ilaria and Harris, Sarah E and Zemunik, Tatijana and Lu, Yingchang and Evangelou, Evangelos and Shah, Nabi and de Borst, Martin H and Mangino, Massimo and Prins, Bram P and Campbell, Archie and Li-Gao, Ruifang and Chauhan, Ganesh and Oldmeadow, Christopher and Abecasis, Goncalo and Abedi, Maryam and Barbieri, Caterina M and Barnes, Michael R and Batini, Chiara and Beilby, John and Blake, Tineka and Boehnke, Michael and Bottinger, Erwin P and Braund, Peter S and Brown, Morris and Brumat, Marco and Campbell, Harry and Chambers, John C and Cocca, Massimiliano and Collins, Francis and Connell, John and Cordell, Heather J and Damman, Jeffrey J and Davies, Gail and de Geus, Eco J and de Mutsert, Ren{\'e}e and Deelen, Joris and Demirkale, Yusuf and Doney, Alex S F and D{\"o}rr, Marcus and Farrall, Martin and Ferreira, Teresa and Fr{\r a}nberg, Mattias and Gao, He and Giedraitis, Vilmantas and Gieger, Christian and Giulianini, Franco and Gow, Alan J and Hamsten, Anders and Harris, Tamara B and Hofman, Albert and Holliday, Elizabeth G and Hui, Jennie and J{\"a}rvelin, Marjo-Riitta and Johansson, {\r A}sa and Johnson, Andrew D and Jousilahti, Pekka and Jula, Antti and K{\"a}h{\"o}nen, Mika and Kathiresan, Sekar and Khaw, Kay-Tee and Kolcic, Ivana and Koskinen, Seppo and Langenberg, Claudia and Larson, Marty and Launer, Lenore J and Lehne, Benjamin and Liewald, David C M and Lin, Li and Lind, Lars and Mach, Fran{\c c}ois and Mamasoula, Chrysovalanto and Menni, Cristina and Mifsud, Borbala and Milaneschi, Yuri and Morgan, Anna and Morris, Andrew D and Morrison, Alanna C and Munson, Peter J and Nandakumar, Priyanka and Nguyen, Quang Tri and Nutile, Teresa and Oldehinkel, Albertine J and Oostra, Ben A and Org, Elin and Padmanabhan, Sandosh and Palotie, Aarno and Par{\'e}, Guillaume and Pattie, Alison and Penninx, Brenda W J H and Poulter, Neil and Pramstaller, Peter P and Raitakari, Olli T and Ren, Meixia and Rice, Kenneth and Ridker, Paul M and Riese, Harri{\"e}tte and Ripatti, Samuli and Robino, Antonietta and Rotter, Jerome I and Rudan, Igor and Saba, Yasaman and Saint Pierre, Aude and Sala, Cinzia F and Sarin, Antti-Pekka and Schmidt, Reinhold and Scott, Rodney and Seelen, Marc A and Shields, Denis C and Siscovick, David and Sorice, Rossella and Stanton, Alice and Stott, David J and Sundstr{\"o}m, Johan and Swertz, Morris and Taylor, Kent D and Thom, Simon and Tzoulaki, Ioanna and Tzourio, Christophe and Uitterlinden, Andr{\'e} G and V{\"o}lker, Uwe and Vollenweider, Peter and Wild, Sarah and Willemsen, Gonneke and Wright, Alan F and Yao, Jie and Th{\'e}riault, S{\'e}bastien and Conen, David and Attia, John and Sever, Peter and Debette, St{\'e}phanie and Mook-Kanamori, Dennis O and Zeggini, Eleftheria and Spector, Tim D and van der Harst, Pim and Palmer, Colin N A and Vergnaud, Anne-Claire and Loos, Ruth J F and Polasek, Ozren and Starr, John M and Girotto, Giorgia and Hayward, Caroline and Kooner, Jaspal S and Lindgren, Cecila M and Vitart, Veronique and Samani, Nilesh J and Tuomilehto, Jaakko and Gyllensten, Ulf and Knekt, Paul and Deary, Ian J and Ciullo, Marina and Elosua, Roberto and Keavney, Bernard D and Hicks, Andrew A and Scott, Robert A and Gasparini, Paolo and Laan, Maris and Liu, Yongmei and Watkins, Hugh and Hartman, Catharina A and Salomaa, Veikko and Toniolo, Daniela and Perola, Markus and Wilson, James F and Schmidt, Helena and Zhao, Jing Hua and Lehtim{\"a}ki, Terho and van Duijn, Cornelia M and Gudnason, Vilmundur and Psaty, Bruce M and Peters, Annette and Rettig, Rainer and James, Alan and Jukema, J Wouter and Strachan, David P and Palmas, Walter and Metspalu, Andres and Ingelsson, Erik and Boomsma, Dorret I and Franco, Oscar H and Bochud, Murielle and Newton-Cheh, Christopher and Munroe, Patricia B and Elliott, Paul and Chasman, Daniel I and Chakravarti, Aravinda and Knight, Joanne and Morris, Andrew P and Levy, Daniel and Tobin, Martin D and Snieder, Harold and Caulfield, Mark J and Ehret, Georg B} } @article {10493, title = {Rare and low-frequency coding variants alter human adult height.}, journal = {Nature}, volume = {542}, year = {2017}, month = {2017 02 09}, pages = {186-190}, abstract = {

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8\%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

}, keywords = {ADAMTS Proteins, Adult, Alleles, Body Height, Cell Adhesion Molecules, Female, Gene Frequency, Genetic Variation, Genome, Human, Glycoproteins, Glycosaminoglycans, Hedgehog Proteins, Humans, Intercellular Signaling Peptides and Proteins, Interferon Regulatory Factors, Interleukin-11 Receptor alpha Subunit, Male, Multifactorial Inheritance, NADPH Oxidase 4, NADPH Oxidases, Phenotype, Pregnancy-Associated Plasma Protein-A, Procollagen N-Endopeptidase, Proteoglycans, Proteolysis, Receptors, Androgen, Somatomedins}, issn = {1476-4687}, doi = {10.1038/nature21039}, author = {Marouli, Eirini and Graff, Mariaelisa and Medina-Gomez, Carolina and Lo, Ken Sin and Wood, Andrew R and Kjaer, Troels R and Fine, Rebecca S and Lu, Yingchang and Schurmann, Claudia and Highland, Heather M and R{\"u}eger, Sina and Thorleifsson, Gudmar and Justice, Anne E and Lamparter, David and Stirrups, Kathleen E and Turcot, Val{\'e}rie and Young, Kristin L and Winkler, Thomas W and Esko, T{\~o}nu and Karaderi, Tugce and Locke, Adam E and Masca, Nicholas G D and Ng, Maggie C Y and Mudgal, Poorva and Rivas, Manuel A and Vedantam, Sailaja and Mahajan, Anubha and Guo, Xiuqing and Abecasis, Goncalo and Aben, Katja K and Adair, Linda S and Alam, Dewan S and Albrecht, Eva and Allin, Kristine H and Allison, Matthew and Amouyel, Philippe and Appel, Emil V and Arveiler, Dominique and Asselbergs, Folkert W and Auer, Paul L and Balkau, Beverley and Banas, Bernhard and Bang, Lia E and Benn, Marianne and Bergmann, Sven and Bielak, Lawrence F and Bl{\"u}her, Matthias and Boeing, Heiner and Boerwinkle, Eric and B{\"o}ger, Carsten A and Bonnycastle, Lori L and Bork-Jensen, Jette and Bots, Michiel L and Bottinger, Erwin P and Bowden, Donald W and Brandslund, Ivan and Breen, Gerome and Brilliant, Murray H and Broer, Linda and Burt, Amber A and Butterworth, Adam S and Carey, David J and Caulfield, Mark J and Chambers, John C and Chasman, Daniel I and Chen, Yii-Der Ida and Chowdhury, Rajiv and Christensen, Cramer and Chu, Audrey Y and Cocca, Massimiliano and Collins, Francis S and Cook, James P and Corley, Janie and Galbany, Jordi Corominas and Cox, Amanda J and Cuellar-Partida, Gabriel and Danesh, John and Davies, Gail and de Bakker, Paul I W and de Borst, Gert J and de Denus, Simon and de Groot, Mark C H and de Mutsert, Ren{\'e}e and Deary, Ian J and Dedoussis, George and Demerath, Ellen W and den Hollander, Anneke I and Dennis, Joe G and Di Angelantonio, Emanuele and Drenos, Fotios and Du, Mengmeng and Dunning, Alison M and Easton, Douglas F and Ebeling, Tapani and Edwards, Todd L and Ellinor, Patrick T and Elliott, Paul and Evangelou, Evangelos and Farmaki, Aliki-Eleni and Faul, Jessica D and Feitosa, Mary F and Feng, Shuang and Ferrannini, Ele and Ferrario, Marco M and Ferri{\`e}res, Jean and Florez, Jose C and Ford, Ian and Fornage, Myriam and Franks, Paul W and Frikke-Schmidt, Ruth and Galesloot, Tessel E and Gan, Wei and Gandin, Ilaria and Gasparini, Paolo and Giedraitis, Vilmantas and Giri, Ayush and Girotto, Giorgia and Gordon, Scott D and Gordon-Larsen, Penny and Gorski, Mathias and Grarup, Niels and Grove, Megan L and Gudnason, Vilmundur and Gustafsson, Stefan and Hansen, Torben and Harris, Kathleen Mullan and Harris, Tamara B and Hattersley, Andrew T and Hayward, Caroline and He, Liang and Heid, Iris M and Heikkil{\"a}, Kauko and Helgeland, {\O}yvind and Hernesniemi, Jussi and Hewitt, Alex W and Hocking, Lynne J and Hollensted, Mette and Holmen, Oddgeir L and Hovingh, G Kees and Howson, Joanna M M and Hoyng, Carel B and Huang, Paul L and Hveem, Kristian and Ikram, M Arfan and Ingelsson, Erik and Jackson, Anne U and Jansson, Jan-H{\r a}kan and Jarvik, Gail P and Jensen, Gorm B and Jhun, Min A and Jia, Yucheng and Jiang, Xuejuan and Johansson, Stefan and J{\o}rgensen, Marit E and J{\o}rgensen, Torben and Jousilahti, Pekka and Jukema, J Wouter and Kahali, Bratati and Kahn, Ren{\'e} S and K{\"a}h{\"o}nen, Mika and Kamstrup, Pia R and Kanoni, Stavroula and Kaprio, Jaakko and Karaleftheri, Maria and Kardia, Sharon L R and Karpe, Fredrik and Kee, Frank and Keeman, Renske and Kiemeney, Lambertus A and Kitajima, Hidetoshi and Kluivers, Kirsten B and Kocher, Thomas and Komulainen, Pirjo and Kontto, Jukka and Kooner, Jaspal S and Kooperberg, Charles and Kovacs, Peter and Kriebel, Jennifer and Kuivaniemi, Helena and K{\"u}ry, S{\'e}bastien and Kuusisto, Johanna and La Bianca, Martina and Laakso, Markku and Lakka, Timo A and Lange, Ethan M and Lange, Leslie A and Langefeld, Carl D and Langenberg, Claudia and Larson, Eric B and Lee, I-Te and Lehtim{\"a}ki, Terho and Lewis, Cora E and Li, Huaixing and Li, Jin and Li-Gao, Ruifang and Lin, Honghuang and Lin, Li-An and Lin, Xu and Lind, Lars and Lindstr{\"o}m, Jaana and Linneberg, Allan and Liu, Yeheng and Liu, Yongmei and Lophatananon, Artitaya and Luan, Jian{\textquoteright}an and Lubitz, Steven A and Lyytik{\"a}inen, Leo-Pekka and Mackey, David A and Madden, Pamela A F and Manning, Alisa K and M{\"a}nnist{\"o}, Satu and Marenne, Ga{\"e}lle and Marten, Jonathan and Martin, Nicholas G and Mazul, Angela L and Meidtner, Karina and Metspalu, Andres and Mitchell, Paul and Mohlke, Karen L and Mook-Kanamori, Dennis O and Morgan, Anna and Morris, Andrew D and Morris, Andrew P and M{\"u}ller-Nurasyid, Martina and Munroe, Patricia B and Nalls, Mike A and Nauck, Matthias and Nelson, Christopher P and Neville, Matt and Nielsen, Sune F and Nikus, Kjell and Nj{\o}lstad, P{\r a}l R and Nordestgaard, B{\o}rge G and Ntalla, Ioanna and O{\textquoteright}Connel, Jeffrey R and Oksa, Heikki and Loohuis, Loes M Olde and Ophoff, Roel A and Owen, Katharine R and Packard, Chris J and Padmanabhan, Sandosh and Palmer, Colin N A and Pasterkamp, Gerard and Patel, Aniruddh P and Pattie, Alison and Pedersen, Oluf and Peissig, Peggy L and Peloso, Gina M and Pennell, Craig E and Perola, Markus and Perry, James A and Perry, John R B and Person, Thomas N and Pirie, Ailith and Polasek, Ozren and Posthuma, Danielle and Raitakari, Olli T and Rasheed, Asif and Rauramaa, Rainer and Reilly, Dermot F and Reiner, Alex P and Renstrom, Frida and Ridker, Paul M and Rioux, John D and Robertson, Neil and Robino, Antonietta and Rolandsson, Olov and Rudan, Igor and Ruth, Katherine S and Saleheen, Danish and Salomaa, Veikko and Samani, Nilesh J and Sandow, Kevin and Sapkota, Yadav and Sattar, Naveed and Schmidt, Marjanka K and Schreiner, Pamela J and Schulze, Matthias B and Scott, Robert A and Segura-Lepe, Marcelo P and Shah, Svati and Sim, Xueling and Sivapalaratnam, Suthesh and Small, Kerrin S and Smith, Albert Vernon and Smith, Jennifer A and Southam, Lorraine and Spector, Timothy D and Speliotes, Elizabeth K and Starr, John M and Steinthorsdottir, Valgerdur and Stringham, Heather M and Stumvoll, Michael and Surendran, Praveen and {\textquoteright}t Hart, Leen M and Tansey, Katherine E and Tardif, Jean-Claude and Taylor, Kent D and Teumer, Alexander and Thompson, Deborah J and Thorsteinsdottir, Unnur and Thuesen, Betina H and T{\"o}njes, Anke and Tromp, Gerard and Trompet, Stella and Tsafantakis, Emmanouil and Tuomilehto, Jaakko and Tybjaerg-Hansen, Anne and Tyrer, Jonathan P and Uher, Rudolf and Uitterlinden, Andr{\'e} G and Ulivi, Sheila and van der Laan, Sander W and Van Der Leij, Andries R and van Duijn, Cornelia M and van Schoor, Natasja M and van Setten, Jessica and Varbo, Anette and Varga, Tibor V and Varma, Rohit and Edwards, Digna R Velez and Vermeulen, Sita H and Vestergaard, Henrik and Vitart, Veronique and Vogt, Thomas F and Vozzi, Diego and Walker, Mark and Wang, Feijie and Wang, Carol A and Wang, Shuai and Wang, Yiqin and Wareham, Nicholas J and Warren, Helen R and Wessel, Jennifer and Willems, Sara M and Wilson, James G and Witte, Daniel R and Woods, Michael O and Wu, Ying and Yaghootkar, Hanieh and Yao, Jie and Yao, Pang and Yerges-Armstrong, Laura M and Young, Robin and Zeggini, Eleftheria and Zhan, Xiaowei and Zhang, Weihua and Zhao, Jing Hua and Zhao, Wei and Zhao, Wei and Zheng, He and Zhou, Wei and Rotter, Jerome I and Boehnke, Michael and Kathiresan, Sekar and McCarthy, Mark I and Willer, Cristen J and Stefansson, Kari and Borecki, Ingrid B and Liu, Dajiang J and North, Kari E and Heard-Costa, Nancy L and Pers, Tune H and Lindgren, Cecilia M and Oxvig, Claus and Kutalik, Zolt{\'a}n and Rivadeneira, Fernando and Loos, Ruth J F and Frayling, Timothy M and Hirschhorn, Joel N and Deloukas, Panos and Lettre, Guillaume} } @article {7696, title = {Directional dominance on stature and cognition in~diverse human populations.}, journal = {Nature}, volume = {523}, year = {2015}, month = {2015 Jul 23}, pages = {459-62}, abstract = {

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs~of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 {\texttimes} 10(-300), 2.1 {\texttimes} 10(-6), 2.5 {\texttimes} 10(-10) and 1.8 {\texttimes} 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months{\textquoteright} less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

}, keywords = {Biological Evolution, Blood Pressure, Body Height, Cholesterol, LDL, Cognition, Cohort Studies, Educational Status, Female, Forced Expiratory Volume, Genome, Human, Homozygote, Humans, Lung Volume Measurements, Male, Phenotype}, issn = {1476-4687}, doi = {10.1038/nature14618}, author = {Joshi, Peter K and Esko, T{\~o}nu and Mattsson, Hannele and Eklund, Niina and Gandin, Ilaria and Nutile, Teresa and Jackson, Anne U and Schurmann, Claudia and Smith, Albert V and Zhang, Weihua and Okada, Yukinori and Stan{\v c}{\'a}kov{\'a}, Alena and Faul, Jessica D and Zhao, Wei and Bartz, Traci M and Concas, Maria Pina and Franceschini, Nora and Enroth, Stefan and Vitart, Veronique and Trompet, Stella and Guo, Xiuqing and Chasman, Daniel I and O{\textquoteright}Connel, Jeffrey R and Corre, Tanguy and Nongmaithem, Suraj S and Chen, Yuning and Mangino, Massimo and Ruggiero, Daniela and Traglia, Michela and Farmaki, Aliki-Eleni and Kacprowski, Tim and Bjonnes, Andrew and van der Spek, Ashley and Wu, Ying and Giri, Anil K and Yanek, Lisa R and Wang, Lihua and Hofer, Edith and Rietveld, Cornelius A and McLeod, Olga and Cornelis, Marilyn C and Pattaro, Cristian and Verweij, Niek and Baumbach, Clemens and Abdellaoui, Abdel and Warren, Helen R and Vuckovic, Dragana and Mei, Hao and Bouchard, Claude and Perry, John R B and Cappellani, Stefania and Mirza, Saira S and Benton, Miles C and Broeckel, Ulrich and Medland, Sarah E and Lind, Penelope A and Malerba, Giovanni and Drong, Alexander and Yengo, Loic and Bielak, Lawrence F and Zhi, Degui and van der Most, Peter J and Shriner, Daniel and M{\"a}gi, Reedik and Hemani, Gibran and Karaderi, Tugce and Wang, Zhaoming and Liu, Tian and Demuth, Ilja and Zhao, Jing Hua and Meng, Weihua and Lataniotis, Lazaros and van der Laan, Sander W and Bradfield, Jonathan P and Wood, Andrew R and Bonnefond, Amelie and Ahluwalia, Tarunveer S and Hall, Leanne M and Salvi, Erika and Yazar, Seyhan and Carstensen, Lisbeth and de Haan, Hugoline G and Abney, Mark and Afzal, Uzma and Allison, Matthew A and Amin, Najaf and Asselbergs, Folkert W and Bakker, Stephan J L and Barr, R Graham and Baumeister, Sebastian E and Benjamin, Daniel J and Bergmann, Sven and Boerwinkle, Eric and Bottinger, Erwin P and Campbell, Archie and Chakravarti, Aravinda and Chan, Yingleong and Chanock, Stephen J and Chen, Constance and Chen, Y-D Ida and Collins, Francis S and Connell, John and Correa, Adolfo and Cupples, L Adrienne and Smith, George Davey and Davies, Gail and D{\"o}rr, Marcus and Ehret, Georg and Ellis, Stephen B and Feenstra, Bjarke and Feitosa, Mary F and Ford, Ian and Fox, Caroline S and Frayling, Timothy M and Friedrich, Nele and Geller, Frank and Scotland, Generation and Gillham-Nasenya, Irina and Gottesman, Omri and Graff, Misa and Grodstein, Francine and Gu, Charles and Haley, Chris and Hammond, Christopher J and Harris, Sarah E and Harris, Tamara B and Hastie, Nicholas D and Heard-Costa, Nancy L and Heikkil{\"a}, Kauko and Hocking, Lynne J and Homuth, Georg and Hottenga, Jouke-Jan and Huang, Jinyan and Huffman, Jennifer E and Hysi, Pirro G and Ikram, M Arfan and Ingelsson, Erik and Joensuu, Anni and Johansson, {\r A}sa and Jousilahti, Pekka and Jukema, J Wouter and K{\"a}h{\"o}nen, Mika and Kamatani, Yoichiro and Kanoni, Stavroula and Kerr, Shona M and Khan, Nazir M and Koellinger, Philipp and Koistinen, Heikki A and Kooner, Manraj K and Kubo, Michiaki and Kuusisto, Johanna and Lahti, Jari and Launer, Lenore J and Lea, Rodney A and Lehne, Benjamin and Lehtim{\"a}ki, Terho and Liewald, David C M and Lind, Lars and Loh, Marie and Lokki, Marja-Liisa and London, Stephanie J and Loomis, Stephanie J and Loukola, Anu and Lu, Yingchang and Lumley, Thomas and Lundqvist, Annamari and M{\"a}nnist{\"o}, Satu and Marques-Vidal, Pedro and Masciullo, Corrado and Matchan, Angela and Mathias, Rasika A and Matsuda, Koichi and Meigs, James B and Meisinger, Christa and Meitinger, Thomas and Menni, Cristina and Mentch, Frank D and Mihailov, Evelin and Milani, Lili and Montasser, May E and Montgomery, Grant W and Morrison, Alanna and Myers, Richard H and Nadukuru, Rajiv and Navarro, Pau and Nelis, Mari and Nieminen, Markku S and Nolte, Ilja M and O{\textquoteright}Connor, George T and Ogunniyi, Adesola and Padmanabhan, Sandosh and Palmas, Walter R and Pankow, James S and Patarcic, Inga and Pavani, Francesca and Peyser, Patricia A and Pietilainen, Kirsi and Poulter, Neil and Prokopenko, Inga and Ralhan, Sarju and Redmond, Paul and Rich, Stephen S and Rissanen, Harri and Robino, Antonietta and Rose, Lynda M and Rose, Richard and Sala, Cinzia and Salako, Babatunde and Salomaa, Veikko and Sarin, Antti-Pekka and Saxena, Richa and Schmidt, Helena and Scott, Laura J and Scott, William R and Sennblad, Bengt and Seshadri, Sudha and Sever, Peter and Shrestha, Smeeta and Smith, Blair H and Smith, Jennifer A and Soranzo, Nicole and Sotoodehnia, Nona and Southam, Lorraine and Stanton, Alice V and Stathopoulou, Maria G and Strauch, Konstantin and Strawbridge, Rona J and Suderman, Matthew J and Tandon, Nikhil and Tang, Sian-Tsun and Taylor, Kent D and Tayo, Bamidele O and T{\"o}glhofer, Anna Maria and Tomaszewski, Maciej and T{\v s}ernikova, Natalia and Tuomilehto, Jaakko and Uitterlinden, Andr{\'e} G and Vaidya, Dhananjay and van Hylckama Vlieg, Astrid and van Setten, Jessica and Vasankari, Tuula and Vedantam, Sailaja and Vlachopoulou, Efthymia and Vozzi, Diego and Vuoksimaa, Eero and Waldenberger, Melanie and Ware, Erin B and Wentworth-Shields, William and Whitfield, John B and Wild, Sarah and Willemsen, Gonneke and Yajnik, Chittaranjan S and Yao, Jie and Zaza, Gianluigi and Zhu, Xiaofeng and Salem, Rany M and Melbye, Mads and Bisgaard, Hans and Samani, Nilesh J and Cusi, Daniele and Mackey, David A and Cooper, Richard S and Froguel, Philippe and Pasterkamp, Gerard and Grant, Struan F A and Hakonarson, Hakon and Ferrucci, Luigi and Scott, Robert A and Morris, Andrew D and Palmer, Colin N A and Dedoussis, George and Deloukas, Panos and Bertram, Lars and Lindenberger, Ulman and Berndt, Sonja I and Lindgren, Cecilia M and Timpson, Nicholas J and T{\"o}njes, Anke and Munroe, Patricia B and S{\o}rensen, Thorkild I A and Rotimi, Charles N and Arnett, Donna K and Oldehinkel, Albertine J and Kardia, Sharon L R and Balkau, Beverley and Gambaro, Giovanni and Morris, Andrew P and Eriksson, Johan G and Wright, Margie J and Martin, Nicholas G and Hunt, Steven C and Starr, John M and Deary, Ian J and Griffiths, Lyn R and Tiemeier, Henning and Pirastu, Nicola and Kaprio, Jaakko and Wareham, Nicholas J and P{\'e}russe, Louis and Wilson, James G and Girotto, Giorgia and Caulfield, Mark J and Raitakari, Olli and Boomsma, Dorret I and Gieger, Christian and van der Harst, Pim and Hicks, Andrew A and Kraft, Peter and Sinisalo, Juha and Knekt, Paul and Johannesson, Magnus and Magnusson, Patrik K E and Hamsten, Anders and Schmidt, Reinhold and Borecki, Ingrid B and Vartiainen, Erkki and Becker, Diane M and Bharadwaj, Dwaipayan and Mohlke, Karen L and Boehnke, Michael and van Duijn, Cornelia M and Sanghera, Dharambir K and Teumer, Alexander and Zeggini, Eleftheria and Metspalu, Andres and Gasparini, Paolo and Ulivi, Sheila and Ober, Carole and Toniolo, Daniela and Rudan, Igor and Porteous, David J and Ciullo, Marina and Spector, Tim D and Hayward, Caroline and Dupuis, Jos{\'e}e and Loos, Ruth J F and Wright, Alan F and Chandak, Giriraj R and Vollenweider, Peter and Shuldiner, Alan R and Ridker, Paul M and Rotter, Jerome I and Sattar, Naveed and Gyllensten, Ulf and North, Kari E and Pirastu, Mario and Psaty, Bruce M and Weir, David R and Laakso, Markku and Gudnason, Vilmundur and Takahashi, Atsushi and Chambers, John C and Kooner, Jaspal S and Strachan, David P and Campbell, Harry and Hirschhorn, Joel N and Perola, Markus and Polasek, Ozren and Wilson, James F} } @article {8066, title = {Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.}, journal = {Nat Genet}, volume = {47}, year = {2015}, month = {2015 Nov}, pages = {1294-303}, abstract = {

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in \~{}70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (\~{}6\% increase in risk per year; P = 3 {\texttimes} 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

}, issn = {1546-1718}, doi = {10.1038/ng.3412}, author = {Day, Felix R and Ruth, Katherine S and Thompson, Deborah J and Lunetta, Kathryn L and Pervjakova, Natalia and Chasman, Daniel I and Stolk, Lisette and Finucane, Hilary K and Sulem, Patrick and Bulik-Sullivan, Brendan and Esko, T{\~o}nu and Johnson, Andrew D and Elks, Cathy E and Franceschini, Nora and He, Chunyan and Altmaier, Elisabeth and Brody, Jennifer A and Franke, Lude L and Huffman, Jennifer E and Keller, Margaux F and McArdle, Patrick F and Nutile, Teresa and Porcu, Eleonora and Robino, Antonietta and Rose, Lynda M and Schick, Ursula M and Smith, Jennifer A and Teumer, Alexander and Traglia, Michela and Vuckovic, Dragana and Yao, Jie and Zhao, Wei and Albrecht, Eva and Amin, Najaf and Corre, Tanguy and Hottenga, Jouke-Jan and Mangino, Massimo and Smith, Albert V and Tanaka, Toshiko and Abecasis, Goncalo R and Andrulis, Irene L and Anton-Culver, Hoda and Antoniou, Antonis C and Arndt, Volker and Arnold, Alice M and Barbieri, Caterina and Beckmann, Matthias W and Beeghly-Fadiel, Alicia and Benitez, Javier and Bernstein, Leslie and Bielinski, Suzette J and Blomqvist, Carl and Boerwinkle, Eric and Bogdanova, Natalia V and Bojesen, Stig E and Bolla, Manjeet K and Borresen-Dale, Anne-Lise and Boutin, Thibaud S and Brauch, Hiltrud and Brenner, Hermann and Br{\"u}ning, Thomas and Burwinkel, Barbara and Campbell, Archie and Campbell, Harry and Chanock, Stephen J and Chapman, J Ross and Chen, Yii-Der Ida and Chenevix-Trench, Georgia and Couch, Fergus J and Coviello, Andrea D and Cox, Angela and Czene, Kamila and Darabi, Hatef and De Vivo, Immaculata and Demerath, Ellen W and Dennis, Joe and Devilee, Peter and D{\"o}rk, Thilo and Dos-Santos-Silva, Isabel and Dunning, Alison M and Eicher, John D and Fasching, Peter A and Faul, Jessica D and Figueroa, Jonine and Flesch-Janys, Dieter and Gandin, Ilaria and Garcia, Melissa E and Garc{\'\i}a-Closas, Montserrat and Giles, Graham G and Girotto, Giorgia G and Goldberg, Mark S and Gonz{\'a}lez-Neira, Anna and Goodarzi, Mark O and Grove, Megan L and Gudbjartsson, Daniel F and Guenel, Pascal and Guo, Xiuqing and Haiman, Christopher A and Hall, Per and Hamann, Ute and Henderson, Brian E and Hocking, Lynne J and Hofman, Albert and Homuth, Georg and Hooning, Maartje J and Hopper, John L and Hu, Frank B and Huang, Jinyan and Humphreys, Keith and Hunter, David J and Jakubowska, Anna and Jones, Samuel E and Kabisch, Maria and Karasik, David and Knight, Julia A and Kolcic, Ivana and Kooperberg, Charles and Kosma, Veli-Matti and Kriebel, Jennifer and Kristensen, Vessela and Lambrechts, Diether and Langenberg, Claudia and Li, Jingmei and Li, Xin and Lindstr{\"o}m, Sara and Liu, Yongmei and Luan, Jian{\textquoteright}an and Lubinski, Jan and M{\"a}gi, Reedik and Mannermaa, Arto and Manz, Judith and Margolin, Sara and Marten, Jonathan and Martin, Nicholas G and Masciullo, Corrado and Meindl, Alfons and Michailidou, Kyriaki and Mihailov, Evelin and Milani, Lili and Milne, Roger L and M{\"u}ller-Nurasyid, Martina and Nalls, Michael and Neale, Benjamin M and Nevanlinna, Heli and Neven, Patrick and Newman, Anne B and Nordestgaard, B{\o}rge G and Olson, Janet E and Padmanabhan, Sandosh and Peterlongo, Paolo and Peters, Ulrike and Petersmann, Astrid and Peto, Julian and Pharoah, Paul D P and Pirastu, Nicola N and Pirie, Ailith and Pistis, Giorgio and Polasek, Ozren and Porteous, David and Psaty, Bruce M and Pylk{\"a}s, Katri and Radice, Paolo and Raffel, Leslie J and Rivadeneira, Fernando and Rudan, Igor and Rudolph, Anja and Ruggiero, Daniela and Sala, Cinzia F and Sanna, Serena and Sawyer, Elinor J and Schlessinger, David and Schmidt, Marjanka K and Schmidt, Frank and Schmutzler, Rita K and Schoemaker, Minouk J and Scott, Robert A and Seynaeve, Caroline M and Simard, Jacques and Sorice, Rossella and Southey, Melissa C and St{\"o}ckl, Doris and Strauch, Konstantin and Swerdlow, Anthony and Taylor, Kent D and Thorsteinsdottir, Unnur and Toland, Amanda E and Tomlinson, Ian and Truong, Therese and Tryggvadottir, Laufey and Turner, Stephen T and Vozzi, Diego and Wang, Qin and Wellons, Melissa and Willemsen, Gonneke and Wilson, James F and Winqvist, Robert and Wolffenbuttel, Bruce B H R and Wright, Alan F and Yannoukakos, Drakoulis and Zemunik, Tatijana and Zheng, Wei and Zygmunt, Marek and Bergmann, Sven and Boomsma, Dorret I and Buring, Julie E and Ferrucci, Luigi and Montgomery, Grant W and Gudnason, Vilmundur and Spector, Tim D and van Duijn, Cornelia M and Alizadeh, Behrooz Z and Ciullo, Marina and Crisponi, Laura and Easton, Douglas F and Gasparini, Paolo P and Gieger, Christian and Harris, Tamara B and Hayward, Caroline and Kardia, Sharon L R and Kraft, Peter and McKnight, Barbara and Metspalu, Andres and Morrison, Alanna C and Reiner, Alex P and Ridker, Paul M and Rotter, Jerome I and Toniolo, Daniela and Uitterlinden, Andr{\'e} G and Ulivi, Sheila and V{\"o}lzke, Henry and Wareham, Nicholas J and Weir, David R and Yerges-Armstrong, Laura M and Price, Alkes L and Stefansson, Kari and Visser, Jenny A and Ong, Ken K and Chang-Claude, Jenny and Murabito, Joanne M and Perry, John R B and Murray, Anna} } @article {1840, title = {Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.}, journal = {Nat Genet}, volume = {43}, year = {2011}, month = {2011 Oct}, pages = {1005-11}, abstract = {

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 {\texttimes} 10(-8) to P = 2.3 {\texttimes} 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

}, keywords = {Arteries, Blood Pressure, Case-Control Studies, Follow-Up Studies, Genetic Loci, Genome-Wide Association Study, Humans, Hypertension, Linkage Disequilibrium, Polymorphism, Single Nucleotide}, issn = {1546-1718}, doi = {10.1038/ng.922}, author = {Wain, Louise V and Verwoert, Germaine C and O{\textquoteright}Reilly, Paul F and Shi, Gang and Johnson, Toby and Johnson, Andrew D and Bochud, Murielle and Rice, Kenneth M and Henneman, Peter and Smith, Albert V and Ehret, Georg B and Amin, Najaf and Larson, Martin G and Mooser, Vincent and Hadley, David and D{\"o}rr, Marcus and Bis, Joshua C and Aspelund, Thor and Esko, T{\~o}nu and Janssens, A Cecile J W and Zhao, Jing Hua and Heath, Simon and Laan, Maris and Fu, Jingyuan and Pistis, Giorgio and Luan, Jian{\textquoteright}an and Arora, Pankaj and Lucas, Gavin and Pirastu, Nicola and Pichler, Irene and Jackson, Anne U and Webster, Rebecca J and Zhang, Feng and Peden, John F and Schmidt, Helena and Tanaka, Toshiko and Campbell, Harry and Igl, Wilmar and Milaneschi, Yuri and Hottenga, Jouke-Jan and Vitart, Veronique and Chasman, Daniel I and Trompet, Stella and Bragg-Gresham, Jennifer L and Alizadeh, Behrooz Z and Chambers, John C and Guo, Xiuqing and Lehtim{\"a}ki, Terho and Kuhnel, Brigitte and Lopez, Lorna M and Polasek, Ozren and Boban, Mladen and Nelson, Christopher P and Morrison, Alanna C and Pihur, Vasyl and Ganesh, Santhi K and Hofman, Albert and Kundu, Suman and Mattace-Raso, Francesco U S and Rivadeneira, Fernando and Sijbrands, Eric J G and Uitterlinden, Andr{\'e} G and Hwang, Shih-Jen and Vasan, Ramachandran S and Wang, Thomas J and Bergmann, Sven and Vollenweider, Peter and Waeber, Gerard and Laitinen, Jaana and Pouta, Anneli and Zitting, Paavo and McArdle, Wendy L and Kroemer, Heyo K and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Glazer, Nicole L and Taylor, Kent D and Harris, Tamara B and Alavere, Helene and Haller, Toomas and Keis, Aime and Tammesoo, Mari-Liis and Aulchenko, Yurii and Barroso, In{\^e}s and Khaw, Kay-Tee and Galan, Pilar and Hercberg, Serge and Lathrop, Mark and Eyheramendy, Susana and Org, Elin and S{\~o}ber, Siim and Lu, Xiaowen and Nolte, Ilja M and Penninx, Brenda W and Corre, Tanguy and Masciullo, Corrado and Sala, Cinzia and Groop, Leif and Voight, Benjamin F and Melander, Olle and O{\textquoteright}Donnell, Christopher J and Salomaa, Veikko and d{\textquoteright}Adamo, Adamo Pio and Fabretto, Antonella and Faletra, Flavio and Ulivi, Sheila and Del Greco, Fabiola M and Facheris, Maurizio and Collins, Francis S and Bergman, Richard N and Beilby, John P and Hung, Joseph and Musk, A William and Mangino, Massimo and Shin, So-Youn and Soranzo, Nicole and Watkins, Hugh and Goel, Anuj and Hamsten, Anders and Gider, Pierre and Loitfelder, Marisa and Zeginigg, Marion and Hernandez, Dena and Najjar, Samer S and Navarro, Pau and Wild, Sarah H and Corsi, Anna Maria and Singleton, Andrew and de Geus, Eco J C and Willemsen, Gonneke and Parker, Alex N and Rose, Lynda M and Buckley, Brendan and Stott, David and Orru, Marco and Uda, Manuela and van der Klauw, Melanie M and Zhang, Weihua and Li, Xinzhong and Scott, James and Chen, Yii-Der Ida and Burke, Gregory L and K{\"a}h{\"o}nen, Mika and Viikari, Jorma and D{\"o}ring, Angela and Meitinger, Thomas and Davies, Gail and Starr, John M and Emilsson, Valur and Plump, Andrew and Lindeman, Jan H and Hoen, Peter A C {\textquoteright}t and K{\"o}nig, Inke R and Felix, Janine F and Clarke, Robert and Hopewell, Jemma C and Ongen, Halit and Breteler, Monique and Debette, St{\'e}phanie and Destefano, Anita L and Fornage, Myriam and Mitchell, Gary F and Smith, Nicholas L and Holm, Hilma and Stefansson, Kari and Thorleifsson, Gudmar and Thorsteinsdottir, Unnur and Samani, Nilesh J and Preuss, Michael and Rudan, Igor and Hayward, Caroline and Deary, Ian J and Wichmann, H-Erich and Raitakari, Olli T and Palmas, Walter and Kooner, Jaspal S and Stolk, Ronald P and Jukema, J Wouter and Wright, Alan F and Boomsma, Dorret I and Bandinelli, Stefania and Gyllensten, Ulf B and Wilson, James F and Ferrucci, Luigi and Schmidt, Reinhold and Farrall, Martin and Spector, Tim D and Palmer, Lyle J and Tuomilehto, Jaakko and Pfeufer, Arne and Gasparini, Paolo and Siscovick, David and Altshuler, David and Loos, Ruth J F and Toniolo, Daniela and Snieder, Harold and Gieger, Christian and Meneton, Pierre and Wareham, Nicholas J and Oostra, Ben A and Metspalu, Andres and Launer, Lenore and Rettig, Rainer and Strachan, David P and Beckmann, Jacques S and Witteman, Jacqueline C M and Erdmann, Jeanette and van Dijk, Ko Willems and Boerwinkle, Eric and Boehnke, Michael and Ridker, Paul M and J{\"a}rvelin, Marjo-Riitta and Chakravarti, Aravinda and Abecasis, Goncalo R and Gudnason, Vilmundur and Newton-Cheh, Christopher and Levy, Daniel and Munroe, Patricia B and Psaty, Bruce M and Caulfield, Mark J and Rao, Dabeeru C and Tobin, Martin D and Elliott, Paul and van Duijn, Cornelia M} }