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

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 × 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 × 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).

%B Am J Hum Genet %V 102 %P 375-400 %8 2018 03 01 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/29455858?dopt=Abstract %R 10.1016/j.ajhg.2018.01.015 %0 Journal Article %J Nature %D 2015 %T Genetic studies of body mass index yield new insights for obesity biology. %A Locke, Adam E %A Kahali, Bratati %A Berndt, Sonja I %A Justice, Anne E %A Pers, Tune H %A Day, Felix R %A Powell, Corey %A Vedantam, Sailaja %A Buchkovich, Martin L %A Yang, Jian %A Croteau-Chonka, Damien C %A Esko, Tõnu %A Fall, Tove %A Ferreira, Teresa %A Gustafsson, Stefan %A Kutalik, Zoltán %A Luan, Jian'an %A Mägi, Reedik %A Randall, Joshua C %A Winkler, Thomas W %A Wood, Andrew R %A Workalemahu, Tsegaselassie %A Faul, Jessica D %A Smith, Jennifer A %A Hua Zhao, Jing %A Zhao, Wei %A Chen, Jin %A Fehrmann, Rudolf %A Hedman, Åsa K %A Karjalainen, Juha %A Schmidt, Ellen M %A Absher, Devin %A Amin, Najaf %A Anderson, Denise %A Beekman, Marian %A Bolton, Jennifer L %A Bragg-Gresham, Jennifer L %A Buyske, Steven %A Demirkan, Ayse %A Deng, Guohong %A Ehret, Georg B %A Feenstra, Bjarke %A Feitosa, Mary F %A Fischer, Krista %A Goel, Anuj %A Gong, Jian %A Jackson, Anne U %A Kanoni, Stavroula %A Kleber, Marcus E %A Kristiansson, Kati %A Lim, Unhee %A Lotay, Vaneet %A Mangino, Massimo %A Mateo Leach, Irene %A Medina-Gomez, Carolina %A Medland, Sarah E %A Nalls, Michael A %A Palmer, Cameron D %A Pasko, Dorota %A Pechlivanis, Sonali %A Peters, Marjolein J %A Prokopenko, Inga %A Shungin, Dmitry %A Stančáková, Alena %A Strawbridge, Rona J %A Ju Sung, Yun %A Tanaka, Toshiko %A Teumer, Alexander %A Trompet, Stella %A van der Laan, Sander W %A van Setten, Jessica %A Van Vliet-Ostaptchouk, Jana V %A Wang, Zhaoming %A Yengo, Loic %A Zhang, Weihua %A Isaacs, Aaron %A Albrecht, Eva %A Arnlöv, Johan %A Arscott, Gillian M %A Attwood, Antony P %A Bandinelli, Stefania %A Barrett, Amy %A Bas, Isabelita N %A Bellis, Claire %A Bennett, Amanda J %A Berne, Christian %A Blagieva, Roza %A Blüher, Matthias %A Böhringer, Stefan %A Bonnycastle, Lori L %A Böttcher, Yvonne %A Boyd, Heather A %A Bruinenberg, Marcel %A Caspersen, Ida H %A Ida Chen, Yii-Der %A Clarke, Robert %A Daw, E Warwick %A de Craen, Anton J M %A Delgado, Graciela %A Dimitriou, Maria %A Doney, Alex S F %A Eklund, Niina %A Estrada, Karol %A Eury, Elodie %A Folkersen, Lasse %A Fraser, Ross M %A Garcia, Melissa E %A Geller, Frank %A Giedraitis, Vilmantas %A Gigante, Bruna %A Go, Alan S %A Golay, Alain %A Goodall, Alison H %A Gordon, Scott D %A Gorski, Mathias %A Grabe, Hans-Jörgen %A Grallert, Harald %A Grammer, Tanja B %A Gräßler, Jürgen %A Grönberg, Henrik %A Groves, Christopher J %A Gusto, Gaëlle %A Haessler, Jeffrey %A Hall, Per %A Haller, Toomas %A Hallmans, Goran %A Hartman, Catharina A %A Hassinen, Maija %A Hayward, Caroline %A Heard-Costa, Nancy L %A Helmer, Quinta %A Hengstenberg, Christian %A Holmen, Oddgeir %A Hottenga, Jouke-Jan %A James, Alan L %A Jeff, Janina M %A Johansson, Åsa %A Jolley, Jennifer %A Juliusdottir, Thorhildur %A Kinnunen, Leena %A Koenig, Wolfgang %A Koskenvuo, Markku %A Kratzer, Wolfgang %A Laitinen, Jaana %A Lamina, Claudia %A Leander, Karin %A Lee, Nanette R %A Lichtner, Peter %A Lind, Lars %A Lindström, Jaana %A Sin Lo, Ken %A Lobbens, Stéphane %A Lorbeer, Roberto %A Lu, Yingchang %A Mach, François %A Magnusson, Patrik K E %A Mahajan, Anubha %A McArdle, Wendy L %A McLachlan, Stela %A Menni, Cristina %A Merger, Sigrun %A Mihailov, Evelin %A Milani, Lili %A Moayyeri, Alireza %A Monda, Keri L %A Morken, Mario A %A Mulas, Antonella %A Müller, Gabriele %A Müller-Nurasyid, Martina %A Musk, Arthur W %A Nagaraja, Ramaiah %A Nöthen, Markus M %A Nolte, Ilja M %A Pilz, Stefan %A Rayner, Nigel W %A Renstrom, Frida %A Rettig, Rainer %A Ried, Janina S %A Ripke, Stephan %A Robertson, Neil R %A Rose, Lynda M %A Sanna, Serena %A Scharnagl, Hubert %A Scholtens, Salome %A Schumacher, Fredrick R %A Scott, William R %A Seufferlein, Thomas %A Shi, Jianxin %A Vernon Smith, Albert %A Smolonska, Joanna %A Stanton, Alice V %A Steinthorsdottir, Valgerdur %A Stirrups, Kathleen %A Stringham, Heather M %A Sundström, Johan %A Swertz, Morris A %A Swift, Amy J %A Syvänen, Ann-Christine %A Tan, Sian-Tsung %A Tayo, Bamidele O %A Thorand, Barbara %A Thorleifsson, Gudmar %A Tyrer, Jonathan P %A Uh, Hae-Won %A Vandenput, Liesbeth %A Verhulst, Frank C %A Vermeulen, Sita H %A Verweij, Niek %A Vonk, Judith M %A Waite, Lindsay L %A Warren, Helen R %A Waterworth, Dawn %A Weedon, Michael N %A Wilkens, Lynne R %A Willenborg, Christina %A Wilsgaard, Tom %A Wojczynski, Mary K %A Wong, Andrew %A Wright, Alan F %A Zhang, Qunyuan %A Brennan, Eoin P %A Choi, Murim %A Dastani, Zari %A Drong, Alexander W %A Eriksson, Per %A Franco-Cereceda, Anders %A Gådin, Jesper R %A Gharavi, Ali G %A Goddard, Michael E %A Handsaker, Robert E %A Huang, Jinyan %A Karpe, Fredrik %A Kathiresan, Sekar %A Keildson, Sarah %A Kiryluk, Krzysztof %A Kubo, Michiaki %A Lee, Jong-Young %A Liang, Liming %A Lifton, Richard P %A Ma, Baoshan %A McCarroll, Steven A %A McKnight, Amy J %A Min, Josine L %A Moffatt, Miriam F %A Montgomery, Grant W %A Murabito, Joanne M %A Nicholson, George %A Nyholt, Dale R %A Okada, Yukinori %A Perry, John R B %A Dorajoo, Rajkumar %A Reinmaa, Eva %A Salem, Rany M %A Sandholm, Niina %A Scott, Robert A %A Stolk, Lisette %A Takahashi, Atsushi %A Tanaka, Toshihiro %A Van't Hooft, Ferdinand M %A Vinkhuyzen, Anna A E %A Westra, Harm-Jan %A Zheng, Wei %A Zondervan, Krina T %A Heath, Andrew C %A Arveiler, Dominique %A Bakker, Stephan J L %A Beilby, John %A Bergman, Richard N %A Blangero, John %A Bovet, Pascal %A Campbell, Harry %A Caulfield, Mark J %A Cesana, Giancarlo %A Chakravarti, Aravinda %A Chasman, Daniel I %A Chines, Peter S %A Collins, Francis S %A Crawford, Dana C %A Cupples, L Adrienne %A Cusi, Daniele %A Danesh, John %A de Faire, Ulf %A den Ruijter, Hester M %A Dominiczak, Anna F %A Erbel, Raimund %A Erdmann, Jeanette %A Eriksson, Johan G %A Farrall, Martin %A Felix, Stephan B %A Ferrannini, Ele %A Ferrières, Jean %A Ford, Ian %A Forouhi, Nita G %A Forrester, Terrence %A Franco, Oscar H %A Gansevoort, Ron T %A Gejman, Pablo V %A Gieger, Christian %A Gottesman, Omri %A Gudnason, Vilmundur %A Gyllensten, Ulf %A Hall, Alistair S %A Harris, Tamara B %A Hattersley, Andrew T %A Hicks, Andrew A %A Hindorff, Lucia A %A Hingorani, Aroon D %A Hofman, Albert %A Homuth, Georg %A Hovingh, G Kees %A Humphries, Steve E %A Hunt, Steven C %A Hyppönen, Elina %A Illig, Thomas %A Jacobs, Kevin B %A Järvelin, Marjo-Riitta %A Jöckel, Karl-Heinz %A Johansen, Berit %A Jousilahti, Pekka %A Jukema, J Wouter %A Jula, Antti M %A Kaprio, Jaakko %A Kastelein, John J P %A Keinanen-Kiukaanniemi, Sirkka M %A Kiemeney, Lambertus A %A Knekt, Paul %A Kooner, Jaspal S %A Kooperberg, Charles %A Kovacs, Peter %A Kraja, Aldi T %A Kumari, Meena %A Kuusisto, Johanna %A Lakka, Timo A %A Langenberg, Claudia %A Le Marchand, Loic %A Lehtimäki, Terho %A Lyssenko, Valeriya %A Männistö, Satu %A Marette, André %A Matise, Tara C %A McKenzie, Colin A %A McKnight, Barbara %A Moll, Frans L %A Morris, Andrew D %A Morris, Andrew P %A Murray, Jeffrey C %A Nelis, Mari %A Ohlsson, Claes %A Oldehinkel, Albertine J %A Ong, Ken K %A Madden, Pamela A F %A Pasterkamp, Gerard %A Peden, John F %A Peters, Annette %A Postma, Dirkje S %A Pramstaller, Peter P %A Price, Jackie F %A Qi, Lu %A Raitakari, Olli T %A Rankinen, Tuomo %A Rao, D C %A Rice, Treva K %A Ridker, Paul M %A Rioux, John D %A Ritchie, Marylyn D %A Rudan, Igor %A Salomaa, Veikko %A Samani, Nilesh J %A Saramies, Jouko %A Sarzynski, Mark A %A Schunkert, Heribert %A Schwarz, Peter E H %A Sever, Peter %A Shuldiner, Alan R %A Sinisalo, Juha %A Stolk, Ronald P %A Strauch, Konstantin %A Tönjes, Anke %A Trégouët, David-Alexandre %A Tremblay, Angelo %A Tremoli, Elena %A Virtamo, Jarmo %A Vohl, Marie-Claude %A Völker, Uwe %A Waeber, Gerard %A Willemsen, Gonneke %A Witteman, Jacqueline C %A Zillikens, M Carola %A Adair, Linda S %A Amouyel, Philippe %A Asselbergs, Folkert W %A Assimes, Themistocles L %A Bochud, Murielle %A Boehm, Bernhard O %A Boerwinkle, Eric %A Bornstein, Stefan R %A Bottinger, Erwin P %A Bouchard, Claude %A Cauchi, Stéphane %A Chambers, John C %A Chanock, Stephen J %A Cooper, Richard S %A de Bakker, Paul I W %A Dedoussis, George %A Ferrucci, Luigi %A Franks, Paul W %A Froguel, Philippe %A Groop, Leif C %A Haiman, Christopher A %A Hamsten, Anders %A Hui, Jennie %A Hunter, David J %A Hveem, Kristian %A Kaplan, Robert C %A Kivimaki, Mika %A Kuh, Diana %A Laakso, Markku %A Liu, Yongmei %A Martin, Nicholas G %A März, Winfried %A Melbye, Mads %A Metspalu, Andres %A Moebus, Susanne %A Munroe, Patricia B %A Njølstad, Inger %A Oostra, Ben A %A Palmer, Colin N A %A Pedersen, Nancy L %A Perola, Markus %A Pérusse, Louis %A Peters, Ulrike %A Power, Chris %A Quertermous, Thomas %A Rauramaa, Rainer %A Rivadeneira, Fernando %A Saaristo, Timo E %A Saleheen, Danish %A Sattar, Naveed %A Schadt, Eric E %A Schlessinger, David %A Slagboom, P Eline %A Snieder, Harold %A Spector, Tim D %A Thorsteinsdottir, Unnur %A Stumvoll, Michael %A Tuomilehto, Jaakko %A Uitterlinden, André G %A Uusitupa, Matti %A van der Harst, Pim %A Walker, Mark %A Wallaschofski, Henri %A Wareham, Nicholas J %A Watkins, Hugh %A Weir, David R %A Wichmann, H-Erich %A Wilson, James F %A Zanen, Pieter %A Borecki, Ingrid B %A Deloukas, Panos %A Fox, Caroline S %A Heid, Iris M %A O'Connell, Jeffrey R %A Strachan, David P %A Stefansson, Kari %A van Duijn, Cornelia M %A Abecasis, Goncalo R %A Franke, Lude %A Frayling, Timothy M %A McCarthy, Mark I %A Visscher, Peter M %A Scherag, André %A Willer, Cristen J %A Boehnke, Michael %A Mohlke, Karen L %A Lindgren, Cecilia M %A Beckmann, Jacques S %A Barroso, Inês %A North, Kari E %A Ingelsson, Erik %A Hirschhorn, Joel N %A Loos, Ruth J F %A Speliotes, Elizabeth K %K Adipogenesis %K Adiposity %K Age Factors %K Body Mass Index %K Continental Population Groups %K Energy Metabolism %K Europe %K Female %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Glutamic Acid %K Humans %K Insulin %K Male %K Obesity %K Polymorphism, Single Nucleotide %K Quantitative Trait Loci %K Synapses %X

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

%B Nature %V 518 %P 197-206 %8 2015 Feb 12 %G eng %N 7538 %1 http://www.ncbi.nlm.nih.gov/pubmed/25673413?dopt=Abstract %R 10.1038/nature14177 %0 Journal Article %J Nature %D 2015 %T New genetic loci link adipose and insulin biology to body fat distribution. %A Shungin, Dmitry %A Winkler, Thomas W %A Croteau-Chonka, Damien C %A Ferreira, Teresa %A Locke, Adam E %A Mägi, Reedik %A Strawbridge, Rona J %A Pers, Tune H %A Fischer, Krista %A Justice, Anne E %A Workalemahu, Tsegaselassie %A Wu, Joseph M W %A Buchkovich, Martin L %A Heard-Costa, Nancy L %A Roman, Tamara S %A Drong, Alexander W %A Song, Ci %A Gustafsson, Stefan %A Day, Felix R %A Esko, Tõnu %A Fall, Tove %A Kutalik, Zoltán %A Luan, Jian'an %A Randall, Joshua C %A Scherag, André %A Vedantam, Sailaja %A Wood, Andrew R %A Chen, Jin %A Fehrmann, Rudolf %A Karjalainen, Juha %A Kahali, Bratati %A Liu, Ching-Ti %A Schmidt, Ellen M %A Absher, Devin %A Amin, Najaf %A Anderson, Denise %A Beekman, Marian %A Bragg-Gresham, Jennifer L %A Buyske, Steven %A Demirkan, Ayse %A Ehret, Georg B %A Feitosa, Mary F %A Goel, Anuj %A Jackson, Anne U %A Johnson, Toby %A Kleber, Marcus E %A Kristiansson, Kati %A Mangino, Massimo %A Mateo Leach, Irene %A Medina-Gomez, Carolina %A Palmer, Cameron D %A Pasko, Dorota %A Pechlivanis, Sonali %A Peters, Marjolein J %A Prokopenko, Inga %A Stančáková, Alena %A Ju Sung, Yun %A Tanaka, Toshiko %A Teumer, Alexander %A Van Vliet-Ostaptchouk, Jana V %A Yengo, Loic %A Zhang, Weihua %A Albrecht, Eva %A Arnlöv, Johan %A Arscott, Gillian M %A Bandinelli, Stefania %A Barrett, Amy %A Bellis, Claire %A Bennett, Amanda J %A Berne, Christian %A Blüher, Matthias %A Böhringer, Stefan %A Bonnet, Fabrice %A Böttcher, Yvonne %A Bruinenberg, Marcel %A Carba, Delia B %A Caspersen, Ida H %A Clarke, Robert %A Daw, E Warwick %A Deelen, Joris %A Deelman, Ewa %A Delgado, Graciela %A Doney, Alex S F %A Eklund, Niina %A Erdos, Michael R %A Estrada, Karol %A Eury, Elodie %A Friedrich, Nele %A Garcia, Melissa E %A Giedraitis, Vilmantas %A Gigante, Bruna %A Go, Alan S %A Golay, Alain %A Grallert, Harald %A Grammer, Tanja B %A Gräßler, Jürgen %A Grewal, Jagvir %A Groves, Christopher J %A Haller, Toomas %A Hallmans, Goran %A Hartman, Catharina A %A Hassinen, Maija %A Hayward, Caroline %A Heikkilä, Kauko %A Herzig, Karl-Heinz %A Helmer, Quinta %A Hillege, Hans L %A Holmen, Oddgeir %A Hunt, Steven C %A Isaacs, Aaron %A Ittermann, Till %A James, Alan L %A Johansson, Ingegerd %A Juliusdottir, Thorhildur %A Kalafati, Ioanna-Panagiota %A Kinnunen, Leena %A Koenig, Wolfgang %A Kooner, Ishminder K %A Kratzer, Wolfgang %A Lamina, Claudia %A Leander, Karin %A Lee, Nanette R %A Lichtner, Peter %A Lind, Lars %A Lindström, Jaana %A Lobbens, Stéphane %A Lorentzon, Mattias %A Mach, François %A Magnusson, Patrik K E %A Mahajan, Anubha %A McArdle, Wendy L %A Menni, Cristina %A Merger, Sigrun %A Mihailov, Evelin %A Milani, Lili %A Mills, Rebecca %A Moayyeri, Alireza %A Monda, Keri L %A Mooijaart, Simon P %A Mühleisen, Thomas W %A Mulas, Antonella %A Müller, Gabriele %A Müller-Nurasyid, Martina %A Nagaraja, Ramaiah %A Nalls, Michael A %A Narisu, Narisu %A Glorioso, Nicola %A Nolte, Ilja M %A Olden, Matthias %A Rayner, Nigel W %A Renstrom, Frida %A Ried, Janina S %A Robertson, Neil R %A Rose, Lynda M %A Sanna, Serena %A Scharnagl, Hubert %A Scholtens, Salome %A Sennblad, Bengt %A Seufferlein, Thomas %A Sitlani, Colleen M %A Vernon Smith, Albert %A Stirrups, Kathleen %A Stringham, Heather M %A Sundström, Johan %A Swertz, Morris A %A Swift, Amy J %A Syvänen, Ann-Christine %A Tayo, Bamidele O %A Thorand, Barbara %A Thorleifsson, Gudmar %A Tomaschitz, Andreas %A Troffa, Chiara %A van Oort, Floor V A %A Verweij, Niek %A Vonk, Judith M %A Waite, Lindsay L %A Wennauer, Roman %A Wilsgaard, Tom %A Wojczynski, Mary K %A Wong, Andrew %A Zhang, Qunyuan %A Hua Zhao, Jing %A Brennan, Eoin P %A Choi, Murim %A Eriksson, Per %A Folkersen, Lasse %A Franco-Cereceda, Anders %A Gharavi, Ali G %A Hedman, Åsa K %A Hivert, Marie-France %A Huang, Jinyan %A Kanoni, Stavroula %A Karpe, Fredrik %A Keildson, Sarah %A Kiryluk, Krzysztof %A Liang, Liming %A Lifton, Richard P %A Ma, Baoshan %A McKnight, Amy J %A McPherson, Ruth %A Metspalu, Andres %A Min, Josine L %A Moffatt, Miriam F %A Montgomery, Grant W %A Murabito, Joanne M %A Nicholson, George %A Nyholt, Dale R %A Olsson, Christian %A Perry, John R B %A Reinmaa, Eva %A Salem, Rany M %A Sandholm, Niina %A Schadt, Eric E %A Scott, Robert A %A Stolk, Lisette %A Vallejo, Edgar E %A Westra, Harm-Jan %A Zondervan, Krina T %A Amouyel, Philippe %A Arveiler, Dominique %A Bakker, Stephan J L %A Beilby, John %A Bergman, Richard N %A Blangero, John %A Brown, Morris J %A Burnier, Michel %A Campbell, Harry %A Chakravarti, Aravinda %A Chines, Peter S %A Claudi-Boehm, Simone %A Collins, Francis S %A Crawford, Dana C %A Danesh, John %A de Faire, Ulf %A de Geus, Eco J C %A Dörr, Marcus %A Erbel, Raimund %A Eriksson, Johan G %A Farrall, Martin %A Ferrannini, Ele %A Ferrières, Jean %A Forouhi, Nita G %A Forrester, Terrence %A Franco, Oscar H %A Gansevoort, Ron T %A Gieger, Christian %A Gudnason, Vilmundur %A Haiman, Christopher A %A Harris, Tamara B %A Hattersley, Andrew T %A Heliövaara, Markku %A Hicks, Andrew A %A Hingorani, Aroon D %A Hoffmann, Wolfgang %A Hofman, Albert %A Homuth, Georg %A Humphries, Steve E %A Hyppönen, Elina %A Illig, Thomas %A Järvelin, Marjo-Riitta %A Johansen, Berit %A Jousilahti, Pekka %A Jula, Antti M %A Kaprio, Jaakko %A Kee, Frank %A Keinanen-Kiukaanniemi, Sirkka M %A Kooner, Jaspal S %A Kooperberg, Charles %A Kovacs, Peter %A Kraja, Aldi T %A Kumari, Meena %A Kuulasmaa, Kari %A Kuusisto, Johanna %A Lakka, Timo A %A Langenberg, Claudia %A Le Marchand, Loic %A Lehtimäki, Terho %A Lyssenko, Valeriya %A Männistö, Satu %A Marette, André %A Matise, Tara C %A McKenzie, Colin A %A McKnight, Barbara %A Musk, Arthur W %A Möhlenkamp, Stefan %A Morris, Andrew D %A Nelis, Mari %A Ohlsson, Claes %A Oldehinkel, Albertine J %A Ong, Ken K %A Palmer, Lyle J %A Penninx, Brenda W %A Peters, Annette %A Pramstaller, Peter P %A Raitakari, Olli T %A Rankinen, Tuomo %A Rao, D C %A Rice, Treva K %A Ridker, Paul M %A Ritchie, Marylyn D %A Rudan, Igor %A Salomaa, Veikko %A Samani, Nilesh J %A Saramies, Jouko %A Sarzynski, Mark A %A Schwarz, Peter E H %A Shuldiner, Alan R %A Staessen, Jan A %A Steinthorsdottir, Valgerdur %A Stolk, Ronald P %A Strauch, Konstantin %A Tönjes, Anke %A Tremblay, Angelo %A Tremoli, Elena %A Vohl, Marie-Claude %A Völker, Uwe %A Vollenweider, Peter %A Wilson, James F %A Witteman, Jacqueline C %A Adair, Linda S %A Bochud, Murielle %A Boehm, Bernhard O %A Bornstein, Stefan R %A Bouchard, Claude %A Cauchi, Stéphane %A Caulfield, Mark J %A Chambers, John C %A Chasman, Daniel I %A Cooper, Richard S %A Dedoussis, George %A Ferrucci, Luigi %A Froguel, Philippe %A Grabe, Hans-Jörgen %A Hamsten, Anders %A Hui, Jennie %A Hveem, Kristian %A Jöckel, Karl-Heinz %A Kivimaki, Mika %A Kuh, Diana %A Laakso, Markku %A Liu, Yongmei %A März, Winfried %A Munroe, Patricia B %A Njølstad, Inger %A Oostra, Ben A %A Palmer, Colin N A %A Pedersen, Nancy L %A Perola, Markus %A Pérusse, Louis %A Peters, Ulrike %A Power, Chris %A Quertermous, Thomas %A Rauramaa, Rainer %A Rivadeneira, Fernando %A Saaristo, Timo E %A Saleheen, Danish %A Sinisalo, Juha %A Slagboom, P Eline %A Snieder, Harold %A Spector, Tim D %A Thorsteinsdottir, Unnur %A Stumvoll, Michael %A Tuomilehto, Jaakko %A Uitterlinden, André G %A Uusitupa, Matti %A van der Harst, Pim %A Veronesi, Giovanni %A Walker, Mark %A Wareham, Nicholas J %A Watkins, Hugh %A Wichmann, H-Erich %A Abecasis, Goncalo R %A Assimes, Themistocles L %A Berndt, Sonja I %A Boehnke, Michael %A Borecki, Ingrid B %A Deloukas, Panos %A Franke, Lude %A Frayling, Timothy M %A Groop, Leif C %A Hunter, David J %A Kaplan, Robert C %A O'Connell, Jeffrey R %A Qi, Lu %A Schlessinger, David %A Strachan, David P %A Stefansson, Kari %A van Duijn, Cornelia M %A Willer, Cristen J %A Visscher, Peter M %A Yang, Jian %A Hirschhorn, Joel N %A Zillikens, M Carola %A McCarthy, Mark I %A Speliotes, Elizabeth K %A North, Kari E %A Fox, Caroline S %A Barroso, Inês %A Franks, Paul W %A Ingelsson, Erik %A Heid, Iris M %A Loos, Ruth J F %A Cupples, L Adrienne %A Morris, Andrew P %A Lindgren, Cecilia M %A Mohlke, Karen L %K Adipocytes %K Adipogenesis %K Adipose Tissue %K Age Factors %K Body Fat Distribution %K Body Mass Index %K Continental Population Groups %K Epigenesis, Genetic %K Europe %K Female %K Genome, Human %K Genome-Wide Association Study %K Humans %K Insulin %K Insulin Resistance %K Male %K Models, Biological %K Neovascularization, Physiologic %K Obesity %K Polymorphism, Single Nucleotide %K Quantitative Trait Loci %K Sex Characteristics %K Transcription, Genetic %K Waist-Hip Ratio %X

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

%B Nature %V 518 %P 187-96 %8 2015 Feb 12 %G eng %N 7538 %1 http://www.ncbi.nlm.nih.gov/pubmed/25673412?dopt=Abstract %R 10.1038/nature14132 %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