%0 Journal Article %J Nat Genet %D 2018 %T Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. %A Evangelou, Evangelos %A Warren, Helen R %A Mosen-Ansorena, David %A Mifsud, Borbala %A Pazoki, Raha %A Gao, He %A Ntritsos, Georgios %A Dimou, Niki %A Cabrera, Claudia P %A Karaman, Ibrahim %A Ng, Fu Liang %A Evangelou, Marina %A Witkowska, Katarzyna %A Tzanis, Evan %A Hellwege, Jacklyn N %A Giri, Ayush %A Velez Edwards, Digna R %A Sun, Yan V %A Cho, Kelly %A Gaziano, J Michael %A Wilson, Peter W F %A Tsao, Philip S %A Kovesdy, Csaba P %A Esko, Tõnu %A Mägi, Reedik %A Milani, Lili %A Almgren, Peter %A Boutin, Thibaud %A Debette, Stéphanie %A Ding, Jun %A Giulianini, Franco %A Holliday, Elizabeth G %A Jackson, Anne U %A Li-Gao, Ruifang %A Lin, Wei-Yu %A Luan, Jian'an %A Mangino, Massimo %A Oldmeadow, Christopher %A Prins, Bram Peter %A Qian, Yong %A Sargurupremraj, Muralidharan %A Shah, Nabi %A Surendran, Praveen %A Thériault, Sébastien %A Verweij, Niek %A Willems, Sara M %A Zhao, Jing-Hua %A Amouyel, Philippe %A Connell, John %A de Mutsert, Renée %A Doney, Alex S F %A Farrall, Martin %A Menni, Cristina %A Morris, Andrew D %A Noordam, Raymond %A Paré, Guillaume %A Poulter, Neil R %A Shields, Denis C %A Stanton, Alice %A Thom, Simon %A Abecasis, Goncalo %A Amin, Najaf %A Arking, Dan E %A Ayers, Kristin L %A Barbieri, Caterina M %A Batini, Chiara %A Bis, Joshua C %A Blake, Tineka %A Bochud, Murielle %A Boehnke, Michael %A Boerwinkle, Eric %A Boomsma, Dorret I %A Bottinger, Erwin P %A Braund, Peter S %A Brumat, Marco %A Campbell, Archie %A Campbell, Harry %A Chakravarti, Aravinda %A Chambers, John C %A Chauhan, Ganesh %A Ciullo, Marina %A Cocca, Massimiliano %A Collins, Francis %A Cordell, Heather J %A Davies, Gail %A de Borst, Martin H %A de Geus, Eco J %A Deary, Ian J %A Deelen, Joris %A del Greco M, Fabiola %A Demirkale, Cumhur Yusuf %A Dörr, Marcus %A Ehret, Georg B %A Elosua, Roberto %A Enroth, Stefan %A Erzurumluoglu, A Mesut %A Ferreira, Teresa %A Frånberg, Mattias %A Franco, Oscar H %A Gandin, Ilaria %A Gasparini, Paolo %A Giedraitis, Vilmantas %A Gieger, Christian %A Girotto, Giorgia %A Goel, Anuj %A Gow, Alan J %A Gudnason, Vilmundur %A Guo, Xiuqing %A Gyllensten, Ulf %A Hamsten, Anders %A Harris, Tamara B %A Harris, Sarah E %A Hartman, Catharina A %A Havulinna, Aki S %A Hicks, Andrew A %A Hofer, Edith %A Hofman, Albert %A Hottenga, Jouke-Jan %A Huffman, Jennifer E %A Hwang, Shih-Jen %A Ingelsson, Erik %A James, Alan %A Jansen, Rick %A Järvelin, Marjo-Riitta %A Joehanes, Roby %A Johansson, Åsa %A Johnson, Andrew D %A Joshi, Peter K %A Jousilahti, Pekka %A Jukema, J Wouter %A Jula, Antti %A Kähönen, Mika %A Kathiresan, Sekar %A Keavney, Bernard D %A Khaw, Kay-Tee %A Knekt, Paul %A Knight, Joanne %A Kolcic, Ivana %A Kooner, Jaspal S %A Koskinen, Seppo %A Kristiansson, Kati %A Kutalik, Zoltán %A Laan, Maris %A Larson, Marty %A Launer, Lenore J %A Lehne, Benjamin %A Lehtimäki, Terho %A Liewald, David C M %A Lin, Li %A Lind, Lars %A Lindgren, Cecilia M %A Liu, Yongmei %A Loos, Ruth J F %A Lopez, Lorna M %A Lu, Yingchang %A Lyytikäinen, Leo-Pekka %A Mahajan, Anubha %A Mamasoula, Chrysovalanto %A Marrugat, Jaume %A Marten, Jonathan %A Milaneschi, Yuri %A Morgan, Anna %A Morris, Andrew P %A Morrison, Alanna C %A Munson, Peter J %A Nalls, Mike A %A Nandakumar, Priyanka %A Nelson, Christopher P %A Niiranen, Teemu %A Nolte, Ilja M %A Nutile, Teresa %A Oldehinkel, Albertine J %A Oostra, Ben A %A O'Reilly, Paul F %A Org, Elin %A Padmanabhan, Sandosh %A Palmas, Walter %A Palotie, Aarno %A Pattie, Alison %A Penninx, Brenda W J H %A Perola, Markus %A Peters, Annette %A Polasek, Ozren %A Pramstaller, Peter P %A Nguyen, Quang Tri %A Raitakari, Olli T %A Ren, Meixia %A Rettig, Rainer %A Rice, Kenneth %A Ridker, Paul M %A Ried, Janina S %A Riese, Harriëtte %A Ripatti, Samuli %A Robino, Antonietta %A Rose, Lynda M %A Rotter, Jerome I %A Rudan, Igor %A Ruggiero, Daniela %A Saba, Yasaman %A Sala, Cinzia F %A Salomaa, Veikko %A Samani, Nilesh J %A Sarin, Antti-Pekka %A Schmidt, Reinhold %A Schmidt, Helena %A Shrine, Nick %A Siscovick, David %A Smith, Albert V %A Snieder, Harold %A Sõber, Siim %A Sorice, Rossella %A Starr, John M %A Stott, David J %A Strachan, David P %A Strawbridge, Rona J %A Sundström, Johan %A Swertz, Morris A %A Taylor, Kent D %A Teumer, Alexander %A Tobin, Martin D %A Tomaszewski, Maciej %A Toniolo, Daniela %A Traglia, Michela %A Trompet, Stella %A Tuomilehto, Jaakko %A Tzourio, Christophe %A Uitterlinden, André G %A Vaez, Ahmad %A van der Most, Peter J %A van Duijn, Cornelia M %A Vergnaud, Anne-Claire %A Verwoert, Germaine C %A Vitart, Veronique %A Völker, Uwe %A Vollenweider, Peter %A Vuckovic, Dragana %A Watkins, Hugh %A Wild, Sarah H %A Willemsen, Gonneke %A Wilson, James F %A Wright, Alan F %A Yao, Jie %A Zemunik, Tatijana %A Zhang, Weihua %A Attia, John R %A Butterworth, Adam S %A Chasman, Daniel I %A Conen, David %A Cucca, Francesco %A Danesh, John %A Hayward, Caroline %A Howson, Joanna M M %A Laakso, Markku %A Lakatta, Edward G %A Langenberg, Claudia %A Melander, Olle %A Mook-Kanamori, Dennis O %A Palmer, Colin N A %A Risch, Lorenz %A Scott, Robert A %A Scott, Rodney J %A Sever, Peter %A Spector, Tim D %A van der Harst, Pim %A Wareham, Nicholas J %A Zeggini, Eleftheria %A Levy, Daniel %A Munroe, Patricia B %A Newton-Cheh, Christopher %A Brown, Morris J %A Metspalu, Andres %A Hung, Adriana M %A O'Donnell, Christopher J %A Edwards, Todd L %A Psaty, Bruce M %A Tzoulaki, Ioanna %A Barnes, Michael R %A Wain, Louise V %A Elliott, Paul %A Caulfield, Mark J %X

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.

%B Nat Genet %V 50 %P 1412-1425 %8 2018 Oct %G eng %N 10 %1 http://www.ncbi.nlm.nih.gov/pubmed/30224653?dopt=Abstract %R 10.1038/s41588-018-0205-x %0 Journal Article %J Nat Commun %D 2017 %T Enrichment of low-frequency functional variants revealed by whole-genome sequencing of multiple isolated European populations. %A Xue, Yali %A Mezzavilla, Massimo %A Haber, Marc %A McCarthy, Shane %A Chen, Yuan %A Narasimhan, Vagheesh %A Gilly, Arthur %A Ayub, Qasim %A Colonna, Vincenza %A Southam, Lorraine %A Finan, Christopher %A Massaia, Andrea %A Chheda, Himanshu %A Palta, Priit %A Ritchie, Graham %A Asimit, Jennifer %A Dedoussis, George %A Gasparini, Paolo %A Palotie, Aarno %A Ripatti, Samuli %A Soranzo, Nicole %A Toniolo, Daniela %A Wilson, James F %A Durbin, Richard %A Tyler-Smith, Chris %A Zeggini, Eleftheria %K European Continental Ancestry Group %K Gene Frequency %K Genetic Variation %K Genetics, Population %K Genome, Human %K Humans %K Polymorphism, Single Nucleotide %K Whole Genome Sequencing %X

The genetic features of isolated populations can boost power in complex-trait association studies, and an in-depth understanding of how their genetic variation has been shaped by their demographic history can help leverage these advantageous characteristics. Here, we perform a comprehensive investigation using 3,059 newly generated low-depth whole-genome sequences from eight European isolates and two matched general populations, together with published data from the 1000 Genomes Project and UK10K. Sequencing data give deeper and richer insights into population demography and genetic characteristics than genotype-chip data, distinguishing related populations more effectively and allowing their functional variants to be studied more fully. We demonstrate relaxation of purifying selection in the isolates, leading to enrichment of rare and low-frequency functional variants, using novel statistics, DVxy and SVxy. We also develop an isolation-index (Isx) that predicts the overall level of such key genetic characteristics and can thus help guide population choice in future complex-trait association studies.

%B Nat Commun %V 8 %P 15927 %8 2017 06 23 %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/28643794?dopt=Abstract %R 10.1038/ncomms15927 %0 Journal Article %J Nat Genet %D 2017 %T Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk. %A Day, Felix R %A Thompson, Deborah J %A Helgason, Hannes %A Chasman, Daniel I %A Finucane, Hilary %A Sulem, Patrick %A Ruth, Katherine S %A Whalen, Sean %A Sarkar, Abhishek K %A Albrecht, Eva %A Altmaier, Elisabeth %A Amini, Marzyeh %A Barbieri, Caterina M %A Boutin, Thibaud %A Campbell, Archie %A Demerath, Ellen %A Giri, Ayush %A He, Chunyan %A Hottenga, Jouke J %A Karlsson, Robert %A Kolcic, Ivana %A Loh, Po-Ru %A Lunetta, Kathryn L %A Mangino, Massimo %A Marco, Brumat %A McMahon, George %A Medland, Sarah E %A Nolte, Ilja M %A Noordam, Raymond %A Nutile, Teresa %A Paternoster, Lavinia %A Perjakova, Natalia %A Porcu, Eleonora %A Rose, Lynda M %A Schraut, Katharina E %A Segrè, Ayellet V %A Smith, Albert V %A Stolk, Lisette %A Teumer, Alexander %A Andrulis, Irene L %A Bandinelli, Stefania %A Beckmann, Matthias W %A Benitez, Javier %A Bergmann, Sven %A Bochud, Murielle %A Boerwinkle, Eric %A Bojesen, Stig E %A Bolla, Manjeet K %A Brand, Judith S %A Brauch, Hiltrud %A Brenner, Hermann %A Broer, Linda %A Brüning, Thomas %A Buring, Julie E %A Campbell, Harry %A Catamo, Eulalia %A Chanock, Stephen %A Chenevix-Trench, Georgia %A Corre, Tanguy %A Couch, Fergus J %A Cousminer, Diana L %A Cox, Angela %A Crisponi, Laura %A Czene, Kamila %A Davey Smith, George %A de Geus, Eco J C N %A de Mutsert, Renée %A De Vivo, Immaculata %A Dennis, Joe %A Devilee, Peter %A Dos-Santos-Silva, Isabel %A Dunning, Alison M %A Eriksson, Johan G %A Fasching, Peter A %A Fernández-Rhodes, Lindsay %A Ferrucci, Luigi %A Flesch-Janys, Dieter %A Franke, Lude %A Gabrielson, Marike %A Gandin, Ilaria %A Giles, Graham G %A Grallert, Harald %A Gudbjartsson, Daniel F %A Guenel, Pascal %A Hall, Per %A Hallberg, Emily %A Hamann, Ute %A Harris, Tamara B %A Hartman, Catharina A %A Heiss, Gerardo %A Hooning, Maartje J %A Hopper, John L %A Hu, Frank %A Hunter, David J %A Ikram, M Arfan %A Im, Hae Kyung %A Järvelin, Marjo-Riitta %A Joshi, Peter K %A Karasik, David %A Kellis, Manolis %A Kutalik, Zoltán %A LaChance, Genevieve %A Lambrechts, Diether %A Langenberg, Claudia %A Launer, Lenore J %A Laven, Joop S E %A Lenarduzzi, Stefania %A Li, Jingmei %A Lind, Penelope A %A Lindström, Sara %A Liu, Yongmei %A Luan, Jian'an %A Mägi, Reedik %A Mannermaa, Arto %A Mbarek, Hamdi %A McCarthy, Mark I %A Meisinger, Christa %A Meitinger, Thomas %A Menni, Cristina %A Metspalu, Andres %A Michailidou, Kyriaki %A Milani, Lili %A Milne, Roger L %A Montgomery, Grant W %A Mulligan, Anna M %A Nalls, Mike A %A Navarro, Pau %A Nevanlinna, Heli %A Nyholt, Dale R %A Oldehinkel, Albertine J %A O'Mara, Tracy A %A Padmanabhan, Sandosh %A Palotie, Aarno %A Pedersen, Nancy %A Peters, Annette %A Peto, Julian %A Pharoah, Paul D P %A Pouta, Anneli %A Radice, Paolo %A Rahman, Iffat %A Ring, Susan M %A Robino, Antonietta %A Rosendaal, Frits R %A Rudan, Igor %A Rueedi, Rico %A Ruggiero, Daniela %A Sala, Cinzia F %A Schmidt, Marjanka K %A Scott, Robert A %A Shah, Mitul %A Sorice, Rossella %A Southey, Melissa C %A Sovio, Ulla %A Stampfer, Meir %A Steri, Maristella %A Strauch, Konstantin %A Tanaka, Toshiko %A Tikkanen, Emmi %A Timpson, Nicholas J %A Traglia, Michela %A Truong, Therese %A Tyrer, Jonathan P %A Uitterlinden, André G %A Edwards, Digna R Velez %A Vitart, Veronique %A Völker, Uwe %A Vollenweider, Peter %A Wang, Qin %A Widen, Elisabeth %A van Dijk, Ko Willems %A Willemsen, Gonneke %A Winqvist, Robert %A Wolffenbuttel, Bruce H R %A Zhao, Jing Hua %A Zoledziewska, Magdalena %A Zygmunt, Marek %A Alizadeh, Behrooz Z %A Boomsma, Dorret I %A Ciullo, Marina %A Cucca, Francesco %A Esko, Tõnu %A Franceschini, Nora %A Gieger, Christian %A Gudnason, Vilmundur %A Hayward, Caroline %A Kraft, Peter %A Lawlor, Debbie A %A Magnusson, Patrik K E %A Martin, Nicholas G %A Mook-Kanamori, Dennis O %A Nohr, Ellen A %A Polasek, Ozren %A Porteous, David %A Price, Alkes L %A Ridker, Paul M %A Snieder, Harold %A Spector, Tim D %A Stöckl, Doris %A Toniolo, Daniela %A Ulivi, Sheila %A Visser, Jenny A %A Völzke, Henry %A Wareham, Nicholas J %A Wilson, James F %A Spurdle, Amanda B %A Thorsteindottir, Unnur %A Pollard, Katherine S %A Easton, Douglas F %A Tung, Joyce Y %A Chang-Claude, Jenny %A Hinds, David %A Murray, Anna %A Murabito, Joanne M %A Stefansson, Kari %A Ong, Ken K %A Perry, John R B %K Adolescent %K Age Factors %K Body Mass Index %K Databases, Genetic %K Female %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Genomic Imprinting %K Humans %K Intercellular Signaling Peptides and Proteins %K Male %K Membrane Proteins %K Menarche %K Neoplasms %K Polymorphism, Single Nucleotide %K Puberty %K Quantitative Trait Loci %K Ribonucleoproteins %K Risk Factors %X

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P < 5 × 10) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.

%B Nat Genet %V 49 %P 834-841 %8 2017 Jun %G eng %N 6 %1 http://www.ncbi.nlm.nih.gov/pubmed/28436984?dopt=Abstract %R 10.1038/ng.3841 %0 Journal Article %J Hypertension %D 2017 %T Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney. %A Wain, Louise V %A Vaez, Ahmad %A Jansen, Rick %A Joehanes, Roby %A van der Most, Peter J %A Erzurumluoglu, A Mesut %A O'Reilly, Paul F %A Cabrera, Claudia P %A Warren, Helen R %A Rose, Lynda M %A Verwoert, Germaine C %A Hottenga, Jouke-Jan %A Strawbridge, Rona J %A Esko, Tõnu %A Arking, Dan E %A Hwang, Shih-Jen %A Guo, Xiuqing %A Kutalik, Zoltán %A Trompet, Stella %A Shrine, Nick %A Teumer, Alexander %A Ried, Janina S %A Bis, Joshua C %A Smith, Albert V %A Amin, Najaf %A Nolte, Ilja M %A Lyytikäinen, Leo-Pekka %A Mahajan, Anubha %A Wareham, Nicholas J %A Hofer, Edith %A Joshi, Peter K %A Kristiansson, Kati %A Traglia, Michela %A Havulinna, Aki S %A Goel, Anuj %A Nalls, Mike A %A Sõber, Siim %A Vuckovic, Dragana %A Luan, Jian'an %A del Greco M, Fabiola %A Ayers, Kristin L %A Marrugat, Jaume %A Ruggiero, Daniela %A Lopez, Lorna M %A Niiranen, Teemu %A Enroth, Stefan %A Jackson, Anne U %A Nelson, Christopher P %A Huffman, Jennifer E %A Zhang, Weihua %A Marten, Jonathan %A Gandin, Ilaria %A Harris, Sarah E %A Zemunik, Tatijana %A Lu, Yingchang %A Evangelou, Evangelos %A Shah, Nabi %A de Borst, Martin H %A Mangino, Massimo %A Prins, Bram P %A Campbell, Archie %A Li-Gao, Ruifang %A Chauhan, Ganesh %A Oldmeadow, Christopher %A Abecasis, Goncalo %A Abedi, Maryam %A Barbieri, Caterina M %A Barnes, Michael R %A Batini, Chiara %A Beilby, John %A Blake, Tineka %A Boehnke, Michael %A Bottinger, Erwin P %A Braund, Peter S %A Brown, Morris %A Brumat, Marco %A Campbell, Harry %A Chambers, John C %A Cocca, Massimiliano %A Collins, Francis %A Connell, John %A Cordell, Heather J %A Damman, Jeffrey J %A Davies, Gail %A de Geus, Eco J %A de Mutsert, Renée %A Deelen, Joris %A Demirkale, Yusuf %A Doney, Alex S F %A Dörr, Marcus %A Farrall, Martin %A Ferreira, Teresa %A Frånberg, Mattias %A Gao, He %A Giedraitis, Vilmantas %A Gieger, Christian %A Giulianini, Franco %A Gow, Alan J %A Hamsten, Anders %A Harris, Tamara B %A Hofman, Albert %A Holliday, Elizabeth G %A Hui, Jennie %A Järvelin, Marjo-Riitta %A Johansson, Åsa %A Johnson, Andrew D %A Jousilahti, Pekka %A Jula, Antti %A Kähönen, Mika %A Kathiresan, Sekar %A Khaw, Kay-Tee %A Kolcic, Ivana %A Koskinen, Seppo %A Langenberg, Claudia %A Larson, Marty %A Launer, Lenore J %A Lehne, Benjamin %A Liewald, David C M %A Lin, Li %A Lind, Lars %A Mach, François %A Mamasoula, Chrysovalanto %A Menni, Cristina %A Mifsud, Borbala %A Milaneschi, Yuri %A Morgan, Anna %A Morris, Andrew D %A Morrison, Alanna C %A Munson, Peter J %A Nandakumar, Priyanka %A Nguyen, Quang Tri %A Nutile, Teresa %A Oldehinkel, Albertine J %A Oostra, Ben A %A Org, Elin %A Padmanabhan, Sandosh %A Palotie, Aarno %A Paré, Guillaume %A Pattie, Alison %A Penninx, Brenda W J H %A Poulter, Neil %A Pramstaller, Peter P %A Raitakari, Olli T %A Ren, Meixia %A Rice, Kenneth %A Ridker, Paul M %A Riese, Harriëtte %A Ripatti, Samuli %A Robino, Antonietta %A Rotter, Jerome I %A Rudan, Igor %A Saba, Yasaman %A Saint Pierre, Aude %A Sala, Cinzia F %A Sarin, Antti-Pekka %A Schmidt, Reinhold %A Scott, Rodney %A Seelen, Marc A %A Shields, Denis C %A Siscovick, David %A Sorice, Rossella %A Stanton, Alice %A Stott, David J %A Sundström, Johan %A Swertz, Morris %A Taylor, Kent D %A Thom, Simon %A Tzoulaki, Ioanna %A Tzourio, Christophe %A Uitterlinden, André G %A Völker, Uwe %A Vollenweider, Peter %A Wild, Sarah %A Willemsen, Gonneke %A Wright, Alan F %A Yao, Jie %A Thériault, Sébastien %A Conen, David %A Attia, John %A Sever, Peter %A Debette, Stéphanie %A Mook-Kanamori, Dennis O %A Zeggini, Eleftheria %A Spector, Tim D %A van der Harst, Pim %A Palmer, Colin N A %A Vergnaud, Anne-Claire %A Loos, Ruth J F %A Polasek, Ozren %A Starr, John M %A Girotto, Giorgia %A Hayward, Caroline %A Kooner, Jaspal S %A Lindgren, Cecila M %A Vitart, Veronique %A Samani, Nilesh J %A Tuomilehto, Jaakko %A Gyllensten, Ulf %A Knekt, Paul %A Deary, Ian J %A Ciullo, Marina %A Elosua, Roberto %A Keavney, Bernard D %A Hicks, Andrew A %A Scott, Robert A %A Gasparini, Paolo %A Laan, Maris %A Liu, Yongmei %A Watkins, Hugh %A Hartman, Catharina A %A Salomaa, Veikko %A Toniolo, Daniela %A Perola, Markus %A Wilson, James F %A Schmidt, Helena %A Zhao, Jing Hua %A Lehtimäki, Terho %A van Duijn, Cornelia M %A Gudnason, Vilmundur %A Psaty, Bruce M %A Peters, Annette %A Rettig, Rainer %A James, Alan %A Jukema, J Wouter %A Strachan, David P %A Palmas, Walter %A Metspalu, Andres %A Ingelsson, Erik %A Boomsma, Dorret I %A Franco, Oscar H %A Bochud, Murielle %A Newton-Cheh, Christopher %A Munroe, Patricia B %A Elliott, Paul %A Chasman, Daniel I %A Chakravarti, Aravinda %A Knight, Joanne %A Morris, Andrew P %A Levy, Daniel %A Tobin, Martin D %A Snieder, Harold %A Caulfield, Mark J %A Ehret, Georg B %X

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.

%B Hypertension %8 2017 Jul 24 %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/28739976?dopt=Abstract %R 10.1161/HYPERTENSIONAHA.117.09438 %0 Journal Article %J Nature %D 2016 %T Genome-wide association study identifies 74 loci associated with educational attainment. %A Okbay, Aysu %A Beauchamp, Jonathan P %A Fontana, Mark Alan %A Lee, James J %A Pers, Tune H %A Rietveld, Cornelius A %A Turley, Patrick %A Chen, Guo-Bo %A Emilsson, Valur %A Meddens, S Fleur W %A Oskarsson, Sven %A Pickrell, Joseph K %A Thom, Kevin %A Timshel, Pascal %A de Vlaming, Ronald %A Abdellaoui, Abdel %A Ahluwalia, Tarunveer S %A Bacelis, Jonas %A Baumbach, Clemens %A Bjornsdottir, Gyda %A Brandsma, Johannes H %A Pina Concas, Maria %A Derringer, Jaime %A Furlotte, Nicholas A %A Galesloot, Tessel E %A Girotto, Giorgia %A Gupta, Richa %A Hall, Leanne M %A Harris, Sarah E %A Hofer, Edith %A Horikoshi, Momoko %A Huffman, Jennifer E %A Kaasik, Kadri %A Kalafati, Ioanna P %A Karlsson, Robert %A Kong, Augustine %A Lahti, Jari %A van der Lee, Sven J %A deLeeuw, Christiaan %A Lind, Penelope A %A Lindgren, Karl-Oskar %A Liu, Tian %A Mangino, Massimo %A Marten, Jonathan %A Mihailov, Evelin %A Miller, Michael B %A van der Most, Peter J %A Oldmeadow, Christopher %A Payton, Antony %A Pervjakova, Natalia %A Peyrot, Wouter J %A Qian, Yong %A Raitakari, Olli %A Rueedi, Rico %A Salvi, Erika %A Schmidt, Börge %A Schraut, Katharina E %A Shi, Jianxin %A Smith, Albert V %A Poot, Raymond A %A St Pourcain, Beate %A Teumer, Alexander %A Thorleifsson, Gudmar %A Verweij, Niek %A Vuckovic, Dragana %A Wellmann, Juergen %A Westra, Harm-Jan %A Yang, Jingyun %A Zhao, Wei %A Zhu, Zhihong %A Alizadeh, Behrooz Z %A Amin, Najaf %A Bakshi, Andrew %A Baumeister, Sebastian E %A Biino, Ginevra %A Bønnelykke, Klaus %A Boyle, Patricia A %A Campbell, Harry %A Cappuccio, Francesco P %A Davies, Gail %A De Neve, Jan-Emmanuel %A Deloukas, Panos %A Demuth, Ilja %A Ding, Jun %A Eibich, Peter %A Eisele, Lewin %A Eklund, Niina %A Evans, David M %A Faul, Jessica D %A Feitosa, Mary F %A Forstner, Andreas J %A Gandin, Ilaria %A Gunnarsson, Bjarni %A Halldórsson, Bjarni V %A Harris, Tamara B %A Heath, Andrew C %A Hocking, Lynne J %A Holliday, Elizabeth G %A Homuth, Georg %A Horan, Michael A %A Hottenga, Jouke-Jan %A de Jager, Philip L %A Joshi, Peter K %A Jugessur, Astanand %A Kaakinen, Marika A %A Kähönen, Mika %A Kanoni, Stavroula %A Keltigangas-Järvinen, Liisa %A Kiemeney, Lambertus A L M %A Kolcic, Ivana %A Koskinen, Seppo %A Kraja, Aldi T %A Kroh, Martin %A Kutalik, Zoltán %A Latvala, Antti %A Launer, Lenore J %A Lebreton, Maël P %A Levinson, Douglas F %A Lichtenstein, Paul %A Lichtner, Peter %A Liewald, David C M %A Loukola, Anu %A Madden, Pamela A %A Mägi, Reedik %A Mäki-Opas, Tomi %A Marioni, Riccardo E %A Marques-Vidal, Pedro %A Meddens, Gerardus A %A McMahon, George %A Meisinger, Christa %A Meitinger, Thomas %A Milaneschi, Yusplitri %A Milani, Lili %A Montgomery, Grant W %A Myhre, Ronny %A Nelson, Christopher P %A Nyholt, Dale R %A Ollier, William E R %A Palotie, Aarno %A Paternoster, Lavinia %A Pedersen, Nancy L %A Petrovic, Katja E %A Porteous, David J %A Räikkönen, Katri %A Ring, Susan M %A Robino, Antonietta %A Rostapshova, Olga %A Rudan, Igor %A Rustichini, Aldo %A Salomaa, Veikko %A Sanders, Alan R %A Sarin, Antti-Pekka %A Schmidt, Helena %A Scott, Rodney J %A Smith, Blair H %A Smith, Jennifer A %A Staessen, Jan A %A Steinhagen-Thiessen, Elisabeth %A Strauch, Konstantin %A Terracciano, Antonio %A Tobin, Martin D %A Ulivi, Sheila %A Vaccargiu, Simona %A Quaye, Lydia %A van Rooij, Frank J A %A Venturini, Cristina %A Vinkhuyzen, Anna A E %A Völker, Uwe %A Völzke, Henry %A Vonk, Judith M %A Vozzi, Diego %A Waage, Johannes %A Ware, Erin B %A Willemsen, Gonneke %A Attia, John R %A Bennett, David A %A Berger, Klaus %A Bertram, Lars %A Bisgaard, Hans %A Boomsma, Dorret I %A Borecki, Ingrid B %A Bültmann, Ute %A Chabris, Christopher F %A Cucca, Francesco %A Cusi, Daniele %A Deary, Ian J %A Dedoussis, George V %A van Duijn, Cornelia M %A Eriksson, Johan G %A Franke, Barbara %A Franke, Lude %A Gasparini, Paolo %A Gejman, Pablo V %A Gieger, Christian %A Grabe, Hans-Jörgen %A Gratten, Jacob %A Groenen, Patrick J F %A Gudnason, Vilmundur %A van der Harst, Pim %A Hayward, Caroline %A Hinds, David A %A Hoffmann, Wolfgang %A Hyppönen, Elina %A Iacono, William G %A Jacobsson, Bo %A Järvelin, Marjo-Riitta %A Jöckel, Karl-Heinz %A Kaprio, Jaakko %A Kardia, Sharon L R %A Lehtimäki, Terho %A Lehrer, Steven F %A Magnusson, Patrik K E %A Martin, Nicholas G %A McGue, Matt %A Metspalu, Andres %A Pendleton, Neil %A Penninx, Brenda W J H %A Perola, Markus %A Pirastu, Nicola %A Pirastu, Mario %A Polasek, Ozren %A Posthuma, Danielle %A Power, Christine %A Province, Michael A %A Samani, Nilesh J %A Schlessinger, David %A Schmidt, Reinhold %A Sørensen, Thorkild I A %A Spector, Tim D %A Stefansson, Kari %A Thorsteinsdottir, Unnur %A Thurik, A Roy %A Timpson, Nicholas J %A Tiemeier, Henning %A Tung, Joyce Y %A Uitterlinden, André G %A Vitart, Veronique %A Vollenweider, Peter %A Weir, David R %A Wilson, James F %A Wright, Alan F %A Conley, Dalton C %A Krueger, Robert F %A Davey Smith, George %A Hofman, Albert %A Laibson, David I %A Medland, Sarah E %A Meyer, Michelle N %A Yang, Jian %A Johannesson, Magnus %A Visscher, Peter M %A Esko, Tõnu %A Koellinger, Philipp D %A Cesarini, David %A Benjamin, Daniel J %K Alzheimer Disease %K Bipolar Disorder %K Brain %K Cognition %K Computational Biology %K Educational Status %K Fetus %K Gene Expression Regulation %K Gene-Environment Interaction %K Genome-Wide Association Study %K Great Britain %K Humans %K Molecular Sequence Annotation %K Polymorphism, Single Nucleotide %K Schizophrenia %X

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.

%B Nature %V 533 %P 539-42 %8 2016 May 26 %G eng %N 7604 %1 http://www.ncbi.nlm.nih.gov/pubmed/27225129?dopt=Abstract %R 10.1038/nature17671 %0 Journal Article %J Nat Genet %D 2016 %T A reference panel of 64,976 haplotypes for genotype imputation. %A McCarthy, Shane %A Das, Sayantan %A Kretzschmar, Warren %A Delaneau, Olivier %A Wood, Andrew R %A Teumer, Alexander %A Kang, Hyun Min %A Fuchsberger, Christian %A Danecek, Petr %A Sharp, Kevin %A Luo, Yang %A Sidore, Carlo %A Kwong, Alan %A Timpson, Nicholas %A Koskinen, Seppo %A Vrieze, Scott %A Scott, Laura J %A Zhang, He %A Mahajan, Anubha %A Veldink, Jan %A Peters, Ulrike %A Pato, Carlos %A van Duijn, Cornelia M %A Gillies, Christopher E %A Gandin, Ilaria %A Mezzavilla, Massimo %A Gilly, Arthur %A Cocca, Massimiliano %A Traglia, Michela %A Angius, Andrea %A Barrett, Jeffrey C %A Boomsma, Dorrett %A Branham, Kari %A Breen, Gerome %A Brummett, Chad M %A Busonero, Fabio %A Campbell, Harry %A Chan, Andrew %A Chen, Sai %A Chew, Emily %A Collins, Francis S %A Corbin, Laura J %A Smith, George Davey %A Dedoussis, George %A Dörr, Marcus %A Farmaki, Aliki-Eleni %A Ferrucci, Luigi %A Forer, Lukas %A Fraser, Ross M %A Gabriel, Stacey %A Levy, Shawn %A Groop, Leif %A Harrison, Tabitha %A Hattersley, Andrew %A Holmen, Oddgeir L %A Hveem, Kristian %A Kretzler, Matthias %A Lee, James C %A McGue, Matt %A Meitinger, Thomas %A Melzer, David %A Min, Josine L %A Mohlke, Karen L %A Vincent, John B %A Nauck, Matthias %A Nickerson, Deborah %A Palotie, Aarno %A Pato, Michele %A Pirastu, Nicola %A McInnis, Melvin %A Richards, J Brent %A Sala, Cinzia %A Salomaa, Veikko %A Schlessinger, David %A Schoenherr, Sebastian %A Slagboom, P Eline %A Small, Kerrin %A Spector, Timothy %A Stambolian, Dwight %A Tuke, Marcus %A Tuomilehto, Jaakko %A Van den Berg, Leonard H %A van Rheenen, Wouter %A Völker, Uwe %A Wijmenga, Cisca %A Toniolo, Daniela %A Zeggini, Eleftheria %A Gasparini, Paolo %A Sampson, Matthew G %A Wilson, James F %A Frayling, Timothy %A de Bakker, Paul I W %A Swertz, Morris A %A McCarroll, Steven %A Kooperberg, Charles %A Dekker, Annelot %A Altshuler, David %A Willer, Cristen %A Iacono, William %A Ripatti, Samuli %A Soranzo, Nicole %A Walter, Klaudia %A Swaroop, Anand %A Cucca, Francesco %A Anderson, Carl A %A Myers, Richard M %A Boehnke, Michael %A McCarthy, Mark I %A Durbin, Richard %X

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.

%B Nat Genet %8 2016 Aug 22 %G ENG %1 http://www.ncbi.nlm.nih.gov/pubmed/27548312?dopt=Abstract %R 10.1038/ng.3643 %0 Journal Article %J Nature %D 2014 %T Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. %A Perry, John R B %A Day, Felix %A Elks, Cathy E %A Sulem, Patrick %A Thompson, Deborah J %A Ferreira, Teresa %A He, Chunyan %A Chasman, Daniel I %A Esko, Tõnu %A Thorleifsson, Gudmar %A Albrecht, Eva %A Ang, Wei Q %A Corre, Tanguy %A Cousminer, Diana L %A Feenstra, Bjarke %A Franceschini, Nora %A Ganna, Andrea %A Johnson, Andrew D %A Kjellqvist, Sanela %A Lunetta, Kathryn L %A McMahon, George %A Nolte, Ilja M %A Paternoster, Lavinia %A Porcu, Eleonora %A Smith, Albert V %A Stolk, Lisette %A Teumer, Alexander %A Tšernikova, Natalia %A Tikkanen, Emmi %A Ulivi, Sheila %A Wagner, Erin K %A Amin, Najaf %A Bierut, Laura J %A Byrne, Enda M %A Hottenga, Jouke-Jan %A Koller, Daniel L %A Mangino, Massimo %A Pers, Tune H %A Yerges-Armstrong, Laura M %A Hua Zhao, Jing %A Andrulis, Irene L %A Anton-Culver, Hoda %A Atsma, Femke %A Bandinelli, Stefania %A Beckmann, Matthias W %A Benitez, Javier %A Blomqvist, Carl %A Bojesen, Stig E %A Bolla, Manjeet K %A Bonanni, Bernardo %A Brauch, Hiltrud %A Brenner, Hermann %A Buring, Julie E %A Chang-Claude, Jenny %A Chanock, Stephen %A Chen, Jinhui %A Chenevix-Trench, Georgia %A Collée, J Margriet %A Couch, Fergus J %A Couper, David %A Coviello, Andrea D %A Cox, Angela %A Czene, Kamila %A d'Adamo, Adamo Pio %A Davey Smith, George %A De Vivo, Immaculata %A Demerath, Ellen W %A Dennis, Joe %A Devilee, Peter %A Dieffenbach, Aida K %A Dunning, Alison M %A Eiriksdottir, Gudny %A Eriksson, Johan G %A Fasching, Peter A %A Ferrucci, Luigi %A Flesch-Janys, Dieter %A Flyger, Henrik %A Foroud, Tatiana %A Franke, Lude %A Garcia, Melissa E %A García-Closas, Montserrat %A Geller, Frank %A de Geus, Eco E J %A Giles, Graham G %A Gudbjartsson, Daniel F %A Gudnason, Vilmundur %A Guenel, Pascal %A Guo, Suiqun %A Hall, Per %A Hamann, Ute %A Haring, Robin %A Hartman, Catharina A %A Heath, Andrew C %A Hofman, Albert %A Hooning, Maartje J %A Hopper, John L %A Hu, Frank B %A Hunter, David J %A Karasik, David %A Kiel, Douglas P %A Knight, Julia A %A Kosma, Veli-Matti %A Kutalik, Zoltán %A Lai, Sandra %A Lambrechts, Diether %A Lindblom, Annika %A Mägi, Reedik %A Magnusson, Patrik K %A Mannermaa, Arto %A Martin, Nicholas G %A Masson, Gisli %A McArdle, Patrick F %A McArdle, Wendy L %A Melbye, Mads %A Michailidou, Kyriaki %A Mihailov, Evelin %A Milani, Lili %A Milne, Roger L %A Nevanlinna, Heli %A Neven, Patrick %A Nohr, Ellen A %A Oldehinkel, Albertine J %A Oostra, Ben A %A Palotie, Aarno %A Peacock, Munro %A Pedersen, Nancy L %A Peterlongo, Paolo %A Peto, Julian %A Pharoah, Paul D P %A Postma, Dirkje S %A Pouta, Anneli %A Pylkäs, Katri %A Radice, Paolo %A Ring, Susan %A Rivadeneira, Fernando %A Robino, Antonietta %A Rose, Lynda M %A Rudolph, Anja %A Salomaa, Veikko %A Sanna, Serena %A Schlessinger, David %A Schmidt, Marjanka K %A Southey, Mellissa C %A Sovio, Ulla %A Stampfer, Meir J %A Stöckl, Doris %A Storniolo, Anna M %A Timpson, Nicholas J %A Tyrer, Jonathan %A Visser, Jenny A %A Vollenweider, Peter %A Völzke, Henry %A Waeber, Gerard %A Waldenberger, Melanie %A Wallaschofski, Henri %A Wang, Qin %A Willemsen, Gonneke %A Winqvist, Robert %A Wolffenbuttel, Bruce H R %A Wright, Margaret J %A Boomsma, Dorret I %A Econs, Michael J %A Khaw, Kay-Tee %A Loos, Ruth J F %A McCarthy, Mark I %A Montgomery, Grant W %A Rice, John P %A Streeten, Elizabeth A %A Thorsteinsdottir, Unnur %A van Duijn, Cornelia M %A Alizadeh, Behrooz Z %A Bergmann, Sven %A Boerwinkle, Eric %A Boyd, Heather A %A Crisponi, Laura %A Gasparini, Paolo %A Gieger, Christian %A Harris, Tamara B %A Ingelsson, Erik %A Järvelin, Marjo-Riitta %A Kraft, Peter %A Lawlor, Debbie %A Metspalu, Andres %A Pennell, Craig E %A Ridker, Paul M %A Snieder, Harold %A Sørensen, Thorkild I A %A Spector, Tim D %A Strachan, David P %A Uitterlinden, André G %A Wareham, Nicholas J %A Widen, Elisabeth %A Zygmunt, Marek %A Murray, Anna %A Easton, Douglas F %A Stefansson, Kari %A Murabito, Joanne M %A Ong, Ken K %K Adolescent %K Age Factors %K Alleles %K Body Mass Index %K Breast Neoplasms %K Cardiovascular Diseases %K Child %K Diabetes Mellitus, Type 2 %K Europe %K Female %K Genetic Loci %K Genome-Wide Association Study %K Genomic Imprinting %K Humans %K Hypothalamo-Hypophyseal System %K Intercellular Signaling Peptides and Proteins %K Male %K Membrane Proteins %K Menarche %K Obesity %K Ovary %K Parents %K Polymorphism, Single Nucleotide %K Potassium Channels, Tandem Pore Domain %K Proteins %K Quantitative Trait Loci %K Receptors, GABA-B %K Receptors, Retinoic Acid %K Ribonucleoproteins %X

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

%B Nature %V 514 %P 92-7 %8 2014 Oct 2 %G eng %N 7520 %1 http://www.ncbi.nlm.nih.gov/pubmed/25231870?dopt=Abstract %R 10.1038/nature13545 %0 Journal Article %J Nat Genet %D 2012 %T Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. %A Stolk, Lisette %A Perry, John R B %A Chasman, Daniel I %A He, Chunyan %A Mangino, Massimo %A Sulem, Patrick %A Barbalic, Maja %A Broer, Linda %A Byrne, Enda M %A Ernst, Florian %A Esko, Tõnu %A Franceschini, Nora %A Gudbjartsson, Daniel F %A Hottenga, Jouke-Jan %A Kraft, Peter %A McArdle, Patrick F %A Porcu, Eleonora %A Shin, So-Youn %A Smith, Albert V %A van Wingerden, Sophie %A Zhai, Guangju %A Zhuang, Wei V %A Albrecht, Eva %A Alizadeh, Behrooz Z %A Aspelund, Thor %A Bandinelli, Stefania %A Lauc, Lovorka Barac %A Beckmann, Jacques S %A Boban, Mladen %A Boerwinkle, Eric %A Broekmans, Frank J %A Burri, Andrea %A Campbell, Harry %A Chanock, Stephen J %A Chen, Constance %A Cornelis, Marilyn C %A Corre, Tanguy %A Coviello, Andrea D %A d'Adamo, Pio %A Davies, Gail %A de Faire, Ulf %A de Geus, Eco J C %A Deary, Ian J %A Dedoussis, George V Z %A Deloukas, Panagiotis %A Ebrahim, Shah %A Eiriksdottir, Gudny %A Emilsson, Valur %A Eriksson, Johan G %A Fauser, Bart C J M %A Ferreli, Liana %A Ferrucci, Luigi %A Fischer, Krista %A Folsom, Aaron R %A Garcia, Melissa E %A Gasparini, Paolo %A Gieger, Christian %A Glazer, Nicole %A Grobbee, Diederick E %A Hall, Per %A Haller, Toomas %A Hankinson, Susan E %A Hass, Merli %A Hayward, Caroline %A Heath, Andrew C %A Hofman, Albert %A Ingelsson, Erik %A Janssens, A Cecile J W %A Johnson, Andrew D %A Karasik, David %A Kardia, Sharon L R %A Keyzer, Jules %A Kiel, Douglas P %A Kolcic, Ivana %A Kutalik, Zoltán %A Lahti, Jari %A Lai, Sandra %A Laisk, Triin %A Laven, Joop S E %A Lawlor, Debbie A %A Liu, Jianjun %A Lopez, Lorna M %A Louwers, Yvonne V %A Magnusson, Patrik K E %A Marongiu, Mara %A Martin, Nicholas G %A Klaric, Irena Martinovic %A Masciullo, Corrado %A McKnight, Barbara %A Medland, Sarah E %A Melzer, David %A Mooser, Vincent %A Navarro, Pau %A Newman, Anne B %A Nyholt, Dale R %A Onland-Moret, N Charlotte %A Palotie, Aarno %A Paré, Guillaume %A Parker, Alex N %A Pedersen, Nancy L %A Peeters, Petra H M %A Pistis, Giorgio %A Plump, Andrew S %A Polasek, Ozren %A Pop, Victor J M %A Psaty, Bruce M %A Räikkönen, Katri %A Rehnberg, Emil %A Rotter, Jerome I %A Rudan, Igor %A Sala, Cinzia %A Salumets, Andres %A Scuteri, Angelo %A Singleton, Andrew %A Smith, Jennifer A %A Snieder, Harold %A Soranzo, Nicole %A Stacey, Simon N %A Starr, John M %A Stathopoulou, Maria G %A Stirrups, Kathleen %A Stolk, Ronald P %A Styrkarsdottir, Unnur %A Sun, Yan V %A Tenesa, Albert %A Thorand, Barbara %A Toniolo, Daniela %A Tryggvadottir, Laufey %A Tsui, Kim %A Ulivi, Sheila %A van Dam, Rob M %A van der Schouw, Yvonne T %A van Gils, Carla H %A van Nierop, Peter %A Vink, Jacqueline M %A Visscher, Peter M %A Voorhuis, Marlies %A Waeber, Gerard %A Wallaschofski, Henri %A Wichmann, H Erich %A Widen, Elisabeth %A Wijnands-van Gent, Colette J M %A Willemsen, Gonneke %A Wilson, James F %A Wolffenbuttel, Bruce H R %A Wright, Alan F %A Yerges-Armstrong, Laura M %A Zemunik, Tatijana %A Zgaga, Lina %A Zillikens, M Carola %A Zygmunt, Marek %A Arnold, Alice M %A Boomsma, Dorret I %A Buring, Julie E %A Crisponi, Laura %A Demerath, Ellen W %A Gudnason, Vilmundur %A Harris, Tamara B %A Hu, Frank B %A Hunter, David J %A Launer, Lenore J %A Metspalu, Andres %A Montgomery, Grant W %A Oostra, Ben A %A Ridker, Paul M %A Sanna, Serena %A Schlessinger, David %A Spector, Tim D %A Stefansson, Kari %A Streeten, Elizabeth A %A Thorsteinsdottir, Unnur %A Uda, Manuela %A Uitterlinden, André G %A van Duijn, Cornelia M %A Völzke, Henry %A Murray, Anna %A Murabito, Joanne M %A Visser, Jenny A %A Lunetta, Kathryn L %K Age Factors %K DNA Helicases %K DNA Primase %K DNA Repair %K DNA Repair Enzymes %K DNA-Directed DNA Polymerase %K European Continental Ancestry Group %K Exodeoxyribonucleases %K Female %K Genetic Loci %K Genome-Wide Association Study %K Humans %K Immunity %K Menopause %K Polymorphism, Single Nucleotide %K Proteins %X

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

%B Nat Genet %V 44 %P 260-8 %8 2012 Mar %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/22267201?dopt=Abstract %R 10.1038/ng.1051 %0 Journal Article %J Nat Genet %D 2010 %T Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. %A Elks, Cathy E %A Perry, John R B %A Sulem, Patrick %A Chasman, Daniel I %A Franceschini, Nora %A He, Chunyan %A Lunetta, Kathryn L %A Visser, Jenny A %A Byrne, Enda M %A Cousminer, Diana L %A Gudbjartsson, Daniel F %A Esko, Tõnu %A Feenstra, Bjarke %A Hottenga, Jouke-Jan %A Koller, Daniel L %A Kutalik, Zoltán %A Lin, Peng %A Mangino, Massimo %A Marongiu, Mara %A McArdle, Patrick F %A Smith, Albert V %A Stolk, Lisette %A van Wingerden, Sophie H %A Zhao, Jing Hua %A Albrecht, Eva %A Corre, Tanguy %A Ingelsson, Erik %A Hayward, Caroline %A Magnusson, Patrik K E %A Smith, Erin N %A Ulivi, Shelia %A Warrington, Nicole M %A Zgaga, Lina %A Alavere, Helen %A Amin, Najaf %A Aspelund, Thor %A Bandinelli, Stefania %A Barroso, Inês %A Berenson, Gerald S %A Bergmann, Sven %A Blackburn, Hannah %A Boerwinkle, Eric %A Buring, Julie E %A Busonero, Fabio %A Campbell, Harry %A Chanock, Stephen J %A Chen, Wei %A Cornelis, Marilyn C %A Couper, David %A Coviello, Andrea D %A d'Adamo, Pio %A de Faire, Ulf %A de Geus, Eco J C %A Deloukas, Panos %A Döring, Angela %A Smith, George Davey %A Easton, Douglas F %A Eiriksdottir, Gudny %A Emilsson, Valur %A Eriksson, Johan %A Ferrucci, Luigi %A Folsom, Aaron R %A Foroud, Tatiana %A Garcia, Melissa %A Gasparini, Paolo %A Geller, Frank %A Gieger, Christian %A Gudnason, Vilmundur %A Hall, Per %A Hankinson, Susan E %A Ferreli, Liana %A Heath, Andrew C %A Hernandez, Dena G %A Hofman, Albert %A Hu, Frank B %A Illig, Thomas %A Järvelin, Marjo-Riitta %A Johnson, Andrew D %A Karasik, David %A Khaw, Kay-Tee %A Kiel, Douglas P %A Kilpeläinen, Tuomas O %A Kolcic, Ivana %A Kraft, Peter %A Launer, Lenore J %A Laven, Joop S E %A Li, Shengxu %A Liu, Jianjun %A Levy, Daniel %A Martin, Nicholas G %A McArdle, Wendy L %A Melbye, Mads %A Mooser, Vincent %A Murray, Jeffrey C %A Murray, Sarah S %A Nalls, Michael A %A Navarro, Pau %A Nelis, Mari %A Ness, Andrew R %A Northstone, Kate %A Oostra, Ben A %A Peacock, Munro %A Palmer, Lyle J %A Palotie, Aarno %A Paré, Guillaume %A Parker, Alex N %A Pedersen, Nancy L %A Peltonen, Leena %A Pennell, Craig E %A Pharoah, Paul %A Polasek, Ozren %A Plump, Andrew S %A Pouta, Anneli %A Porcu, Eleonora %A Rafnar, Thorunn %A Rice, John P %A Ring, Susan M %A Rivadeneira, Fernando %A Rudan, Igor %A Sala, Cinzia %A Salomaa, Veikko %A Sanna, Serena %A Schlessinger, David %A Schork, Nicholas J %A Scuteri, Angelo %A Segrè, Ayellet V %A Shuldiner, Alan R %A Soranzo, Nicole %A Sovio, Ulla %A Srinivasan, Sathanur R %A Strachan, David P %A Tammesoo, Mar-Liis %A Tikkanen, Emmi %A Toniolo, Daniela %A Tsui, Kim %A Tryggvadottir, Laufey %A Tyrer, Jonathon %A Uda, Manuela %A van Dam, Rob M %A van Meurs, Joyce B J %A Vollenweider, Peter %A Waeber, Gerard %A Wareham, Nicholas J %A Waterworth, Dawn M %A Weedon, Michael N %A Wichmann, H Erich %A Willemsen, Gonneke %A Wilson, James F %A Wright, Alan F %A Young, Lauren %A Zhai, Guangju %A Zhuang, Wei Vivian %A Bierut, Laura J %A Boomsma, Dorret I %A Boyd, Heather A %A Crisponi, Laura %A Demerath, Ellen W %A van Duijn, Cornelia M %A Econs, Michael J %A Harris, Tamara B %A Hunter, David J %A Loos, Ruth J F %A Metspalu, Andres %A Montgomery, Grant W %A Ridker, Paul M %A Spector, Tim D %A Streeten, Elizabeth A %A Stefansson, Kari %A Thorsteinsdottir, Unnur %A Uitterlinden, André G %A Widen, Elisabeth %A Murabito, Joanne M %A Ong, Ken K %A Murray, Anna %K Adolescent %K Aging %K Body Height %K Body Size %K Child %K DNA Copy Number Variations %K Female %K Genetic Loci %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Humans %K Inheritance Patterns %K Menarche %K Obesity %K Polymorphism, Single Nucleotide %K Quantitative Trait Loci %K Reproducibility of Results %K Time Factors %X

To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

%B Nat Genet %V 42 %P 1077-85 %8 2010 Dec %G eng %N 12 %1 http://www.ncbi.nlm.nih.gov/pubmed/21102462?dopt=Abstract %R 10.1038/ng.714