@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 {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 {8484, title = {Genome-wide association study identifies 74 loci associated with educational attainment.}, journal = {Nature}, volume = {533}, year = {2016}, month = {2016 May 26}, pages = {539-42}, abstract = {

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20\% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

}, keywords = {Alzheimer Disease, Bipolar Disorder, Brain, Cognition, Computational Biology, Educational Status, Fetus, Gene Expression Regulation, Gene-Environment Interaction, Genome-Wide Association Study, Great Britain, Humans, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Schizophrenia}, issn = {1476-4687}, doi = {10.1038/nature17671}, author = {Okbay, Aysu and Beauchamp, Jonathan P and Fontana, Mark Alan and Lee, James J and Pers, Tune H and Rietveld, Cornelius A and Turley, Patrick and Chen, Guo-Bo and Emilsson, Valur and Meddens, S Fleur W and Oskarsson, Sven and Pickrell, Joseph K and Thom, Kevin and Timshel, Pascal and de Vlaming, Ronald and Abdellaoui, Abdel and Ahluwalia, Tarunveer S and Bacelis, Jonas and Baumbach, Clemens and Bjornsdottir, Gyda and Brandsma, Johannes H and Pina Concas, Maria and Derringer, Jaime and Furlotte, Nicholas A and Galesloot, Tessel E and Girotto, Giorgia and Gupta, Richa and Hall, Leanne M and Harris, Sarah E and Hofer, Edith and Horikoshi, Momoko and Huffman, Jennifer E and Kaasik, Kadri and Kalafati, Ioanna P and Karlsson, Robert and Kong, Augustine and Lahti, Jari and van der Lee, Sven J and deLeeuw, Christiaan and Lind, Penelope A and Lindgren, Karl-Oskar and Liu, Tian and Mangino, Massimo and Marten, Jonathan and Mihailov, Evelin and Miller, Michael B and van der Most, Peter J and Oldmeadow, Christopher and Payton, Antony and Pervjakova, Natalia and Peyrot, Wouter J and Qian, Yong and Raitakari, Olli and Rueedi, Rico and Salvi, Erika and Schmidt, B{\"o}rge and Schraut, Katharina E and Shi, Jianxin and Smith, Albert V and Poot, Raymond A and St Pourcain, Beate and Teumer, Alexander and Thorleifsson, Gudmar and Verweij, Niek and Vuckovic, Dragana and Wellmann, Juergen and Westra, Harm-Jan and Yang, Jingyun and Zhao, Wei and Zhu, Zhihong and Alizadeh, Behrooz Z and Amin, Najaf and Bakshi, Andrew and Baumeister, Sebastian E and Biino, Ginevra and B{\o}nnelykke, Klaus and Boyle, Patricia A and Campbell, Harry and Cappuccio, Francesco P and Davies, Gail and De Neve, Jan-Emmanuel and Deloukas, Panos and Demuth, Ilja and Ding, Jun and Eibich, Peter and Eisele, Lewin and Eklund, Niina and Evans, David M and Faul, Jessica D and Feitosa, Mary F and Forstner, Andreas J and Gandin, Ilaria and Gunnarsson, Bjarni and Halld{\'o}rsson, Bjarni V and Harris, Tamara B and Heath, Andrew C and Hocking, Lynne J and Holliday, Elizabeth G and Homuth, Georg and Horan, Michael A and Hottenga, Jouke-Jan and de Jager, Philip L and Joshi, Peter K and Jugessur, Astanand and Kaakinen, Marika A and K{\"a}h{\"o}nen, Mika and Kanoni, Stavroula and Keltigangas-J{\"a}rvinen, Liisa and Kiemeney, Lambertus A L M and Kolcic, Ivana and Koskinen, Seppo and Kraja, Aldi T and Kroh, Martin and Kutalik, Zolt{\'a}n and Latvala, Antti and Launer, Lenore J and Lebreton, Ma{\"e}l P and Levinson, Douglas F and Lichtenstein, Paul and Lichtner, Peter and Liewald, David C M and Loukola, Anu and Madden, Pamela A and M{\"a}gi, Reedik and M{\"a}ki-Opas, Tomi and Marioni, Riccardo E and Marques-Vidal, Pedro and Meddens, Gerardus A and McMahon, George and Meisinger, Christa and Meitinger, Thomas and Milaneschi, Yusplitri and Milani, Lili and Montgomery, Grant W and Myhre, Ronny and Nelson, Christopher P and Nyholt, Dale R and Ollier, William E R and Palotie, Aarno and Paternoster, Lavinia and Pedersen, Nancy L and Petrovic, Katja E and Porteous, David J and R{\"a}ikk{\"o}nen, Katri and Ring, Susan M and Robino, Antonietta and Rostapshova, Olga and Rudan, Igor and Rustichini, Aldo and Salomaa, Veikko and Sanders, Alan R and Sarin, Antti-Pekka and Schmidt, Helena and Scott, Rodney J and Smith, Blair H and Smith, Jennifer A and Staessen, Jan A and Steinhagen-Thiessen, Elisabeth and Strauch, Konstantin and Terracciano, Antonio and Tobin, Martin D and Ulivi, Sheila and Vaccargiu, Simona and Quaye, Lydia and van Rooij, Frank J A and Venturini, Cristina and Vinkhuyzen, Anna A E and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Vonk, Judith M and Vozzi, Diego and Waage, Johannes and Ware, Erin B and Willemsen, Gonneke and Attia, John R and Bennett, David A and Berger, Klaus and Bertram, Lars and Bisgaard, Hans and Boomsma, Dorret I and Borecki, Ingrid B and B{\"u}ltmann, Ute and Chabris, Christopher F and Cucca, Francesco and Cusi, Daniele and Deary, Ian J and Dedoussis, George V and van Duijn, Cornelia M and Eriksson, Johan G and Franke, Barbara and Franke, Lude and Gasparini, Paolo and Gejman, Pablo V and Gieger, Christian and Grabe, Hans-J{\"o}rgen and Gratten, Jacob and Groenen, Patrick J F and Gudnason, Vilmundur and van der Harst, Pim and Hayward, Caroline and Hinds, David A and Hoffmann, Wolfgang and Hypp{\"o}nen, Elina and Iacono, William G and Jacobsson, Bo and J{\"a}rvelin, Marjo-Riitta and J{\"o}ckel, Karl-Heinz and Kaprio, Jaakko and Kardia, Sharon L R and Lehtim{\"a}ki, Terho and Lehrer, Steven F and Magnusson, Patrik K E and Martin, Nicholas G and McGue, Matt and Metspalu, Andres and Pendleton, Neil and Penninx, Brenda W J H and Perola, Markus and Pirastu, Nicola and Pirastu, Mario and Polasek, Ozren and Posthuma, Danielle and Power, Christine and Province, Michael A and Samani, Nilesh J and Schlessinger, David and Schmidt, Reinhold and S{\o}rensen, Thorkild I A and Spector, Tim D and Stefansson, Kari and Thorsteinsdottir, Unnur and Thurik, A Roy and Timpson, Nicholas J and Tiemeier, Henning and Tung, Joyce Y and Uitterlinden, Andr{\'e} G and Vitart, Veronique and Vollenweider, Peter and Weir, David R and Wilson, James F and Wright, Alan F and Conley, Dalton C and Krueger, Robert F and Davey Smith, George and Hofman, Albert and Laibson, David I and Medland, Sarah E and Meyer, Michelle N and Yang, Jian and Johannesson, Magnus and Visscher, Peter M and Esko, T{\~o}nu and Koellinger, Philipp D and Cesarini, David and Benjamin, Daniel J} } @article {8526, title = {A reference panel of 64,976 haplotypes for genotype imputation.}, journal = {Nat Genet}, year = {2016}, month = {2016 Aug 22}, abstract = {

We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1\% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.

}, issn = {1546-1718}, doi = {10.1038/ng.3643}, author = {McCarthy, Shane and Das, Sayantan and Kretzschmar, Warren and Delaneau, Olivier and Wood, Andrew R and Teumer, Alexander and Kang, Hyun Min and Fuchsberger, Christian and Danecek, Petr and Sharp, Kevin and Luo, Yang and Sidore, Carlo and Kwong, Alan and Timpson, Nicholas and Koskinen, Seppo and Vrieze, Scott and Scott, Laura J and Zhang, He and Mahajan, Anubha and Veldink, Jan and Peters, Ulrike and Pato, Carlos and van Duijn, Cornelia M and Gillies, Christopher E and Gandin, Ilaria and Mezzavilla, Massimo and Gilly, Arthur and Cocca, Massimiliano and Traglia, Michela and Angius, Andrea and Barrett, Jeffrey C and Boomsma, Dorrett and Branham, Kari and Breen, Gerome and Brummett, Chad M and Busonero, Fabio and Campbell, Harry and Chan, Andrew and Chen, Sai and Chew, Emily and Collins, Francis S and Corbin, Laura J and Smith, George Davey and Dedoussis, George and D{\"o}rr, Marcus and Farmaki, Aliki-Eleni and Ferrucci, Luigi and Forer, Lukas and Fraser, Ross M and Gabriel, Stacey and Levy, Shawn and Groop, Leif and Harrison, Tabitha and Hattersley, Andrew and Holmen, Oddgeir L and Hveem, Kristian and Kretzler, Matthias and Lee, James C and McGue, Matt and Meitinger, Thomas and Melzer, David and Min, Josine L and Mohlke, Karen L and Vincent, John B and Nauck, Matthias and Nickerson, Deborah and Palotie, Aarno and Pato, Michele and Pirastu, Nicola and McInnis, Melvin and Richards, J Brent and Sala, Cinzia and Salomaa, Veikko and Schlessinger, David and Schoenherr, Sebastian and Slagboom, P Eline and Small, Kerrin and Spector, Timothy and Stambolian, Dwight and Tuke, Marcus and Tuomilehto, Jaakko and Van den Berg, Leonard H and van Rheenen, Wouter and V{\"o}lker, Uwe and Wijmenga, Cisca and Toniolo, Daniela and Zeggini, Eleftheria and Gasparini, Paolo and Sampson, Matthew G and Wilson, James F and Frayling, Timothy and de Bakker, Paul I W and Swertz, Morris A and McCarroll, Steven and Kooperberg, Charles and Dekker, Annelot and Altshuler, David and Willer, Cristen and Iacono, William and Ripatti, Samuli and Soranzo, Nicole and Walter, Klaudia and Swaroop, Anand and Cucca, Francesco and Anderson, Carl A and Myers, Richard M and Boehnke, Michael and McCarthy, Mark I and Durbin, Richard} } @article {1958, title = {Evidence of inbreeding depression on human height.}, journal = {PLoS Genet}, volume = {8}, year = {2012}, month = {2012}, pages = {e1002655}, abstract = {

Stature is a classical and highly heritable complex trait, with 80\%-90\% of variation explained by genetic factors. In recent years, genome-wide association studies (GWAS) have successfully identified many common additive variants influencing human height; however, little attention has been given to the potential role of recessive genetic effects. Here, we investigated genome-wide recessive effects by an analysis of inbreeding depression on adult height in over 35,000 people from 21 different population samples. We found a highly significant inverse association between height and genome-wide homozygosity, equivalent to a height reduction of up to 3 cm in the offspring of first cousins compared with the offspring of unrelated individuals, an effect which remained after controlling for the effects of socio-economic status, an important confounder (χ(2) = 83.89, df = 1; p = 5.2 {\texttimes} 10(-20)). There was, however, a high degree of heterogeneity among populations: whereas the direction of the effect was consistent across most population samples, the effect size differed significantly among populations. It is likely that this reflects true biological heterogeneity: whether or not an effect can be observed will depend on both the variance in homozygosity in the population and the chance inheritance of individual recessive genotypes. These results predict that multiple, rare, recessive variants influence human height. Although this exploratory work focuses on height alone, the methodology developed is generally applicable to heritable quantitative traits (QT), paving the way for an investigation into inbreeding effects, and therefore genetic architecture, on a range of QT of biomedical importance.

}, keywords = {Adult, Aged, Body Height, Consanguinity, Databases, Genetic, Family, Female, Genes, Recessive, Genetic Heterogeneity, Genome-Wide Association Study, Homozygote, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1002655}, author = {McQuillan, Ruth and Eklund, Niina and Pirastu, Nicola and Kuningas, Maris and McEvoy, Brian P and Esko, T{\~o}nu and Corre, Tanguy and Davies, Gail and Kaakinen, Marika and Lyytik{\"a}inen, Leo-Pekka and Kristiansson, Kati and Havulinna, Aki S and G{\"o}gele, Martin and Vitart, Veronique and Tenesa, Albert and Aulchenko, Yurii and Hayward, Caroline and Johansson, {\r A}sa and Boban, Mladen and Ulivi, Sheila and Robino, Antonietta and Boraska, Vesna and Igl, Wilmar and Wild, Sarah H and Zgaga, Lina and Amin, Najaf and Theodoratou, Evropi and Polasek, Ozren and Girotto, Giorgia and Lopez, Lorna M and Sala, Cinzia and Lahti, Jari and Laatikainen, Tiina and Prokopenko, Inga and Kals, Mart and Viikari, Jorma and Yang, Jian and Pouta, Anneli and Estrada, Karol and Hofman, Albert and Freimer, Nelson and Martin, Nicholas G and K{\"a}h{\"o}nen, Mika and Milani, Lili and Heli{\"o}vaara, Markku and Vartiainen, Erkki and R{\"a}ikk{\"o}nen, Katri and Masciullo, Corrado and Starr, John M and Hicks, Andrew A and Esposito, Laura and Kolcic, Ivana and Farrington, Susan M and Oostra, Ben and Zemunik, Tatijana and Campbell, Harry and Kirin, Mirna and Pehlic, Marina and Faletra, Flavio and Porteous, David and Pistis, Giorgio and Widen, Elisabeth and Salomaa, Veikko and Koskinen, Seppo and Fischer, Krista and Lehtim{\"a}ki, Terho and Heath, Andrew and McCarthy, Mark I and Rivadeneira, Fernando and Montgomery, Grant W and Tiemeier, Henning and Hartikainen, Anna-Liisa and Madden, Pamela A F and d{\textquoteright}Adamo, Pio and Hastie, Nicholas D and Gyllensten, Ulf and Wright, Alan F and van Duijn, Cornelia M and Dunlop, Malcolm and Rudan, Igor and Gasparini, Paolo and Pramstaller, Peter P and Deary, Ian J and Toniolo, Daniela and Eriksson, Johan G and Jula, Antti and Raitakari, Olli T and Metspalu, Andres and Perola, Markus and J{\"a}rvelin, Marjo-Riitta and Uitterlinden, Andr{\'e} and Visscher, Peter M and Wilson, James F} }