TY - JOUR T1 - A meta-analysis of genome-wide association studies identifies multiple longevity genes. JF - Nature Communications Y1 - 2019 A1 - Deelen, Joris A1 - Daniel S Evans A1 - Dan E Arking A1 - Tesi, Niccolò A1 - Nygaard, Marianne A1 - Liu, Xiaomin A1 - Wojczynski, Mary K A1 - Biggs, Mary L A1 - van der Spek, Ashley A1 - Atzmon, Gil A1 - Erin B Ware A1 - Sarnowski, Chloé A1 - Albert Vernon Smith A1 - Seppälä, Ilkka A1 - Cordell, Heather J A1 - Dose, Janina A1 - Amin, Najaf A1 - Alice M. Arnold A1 - Kristin L. Ayers A1 - Barzilai, Nir A1 - Becker, Elizabeth J A1 - Beekman, Marian A1 - Blanché, Hélène A1 - Christensen, Kaare A1 - Christiansen, Lene A1 - Collerton, Joanna C A1 - Cubaynes, Sarah A1 - Steven R Cummings A1 - Davies, Karen A1 - Debrabant, Birgit A1 - Deleuze, Jean-François A1 - Duncan, Rachel A1 - Jessica Faul A1 - Franceschi, Claudio A1 - Galan, Pilar A1 - Gudnason, Vilmundur A1 - Tamara B Harris A1 - Huisman, Martijn A1 - Hurme, Mikko A A1 - Jagger, Carol A1 - Jansen, Iris A1 - Jylhä, Marja A1 - Kähönen, Mika A1 - Karasik, David A1 - Sharon L R Kardia A1 - Kingston, Andrew A1 - Kirkwood, Thomas B L A1 - Lenore J Launer A1 - Lehtimäki, Terho A1 - Lieb, Wolfgang A1 - Lyytikäinen, Leo-Pekka A1 - Martin-Ruiz, Carmen A1 - Min, Junxia A1 - Nebel, Almut A1 - Anne B Newman A1 - Nie, Chao A1 - Nohr, Ellen A A1 - Orwoll, Eric S A1 - Thomas T Perls A1 - Province, Michael A A1 - Psaty, Bruce M A1 - Olli T Raitakari A1 - Reinders, Marcel J T A1 - Robine, Jean-Marie A1 - Rotter, Jerome I A1 - Sebastiani, Paola A1 - Jennifer A Smith A1 - Sørensen, Thorkild I A A1 - Kent D Taylor A1 - André G Uitterlinden A1 - van der Flier, Wiesje A1 - Sven J van der Lee A1 - Cornelia M van Duijn A1 - van Heemst, Diana A1 - James W Vaupel A1 - David R Weir A1 - Ye, Kenny A1 - Zeng, Yi A1 - Zheng, Wanlin A1 - Holstege, Henne A1 - Douglas P Kiel A1 - Kathryn L Lunetta A1 - Eline P Slagboom A1 - Joanne M Murabito KW - genes KW - Genome-Wide Association Study KW - GWA KW - longevity genes KW - meta-analysis AB -

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

VL - 10 UR - https://www.ncbi.nlm.nih.gov/pubmed/31413261 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/31413261?dopt=Abstract ER - TY - JOUR T1 - Genome-wide analysis identifies 12 loci influencing human reproductive behavior. JF - Nat Genet Y1 - 2016 A1 - Nicola Barban A1 - Jansen, Rick A1 - de Vlaming, Ronald A1 - Vaez, Ahmad A1 - Mandemakers, Jornt J A1 - Felix C Tropf A1 - Shen, Xia A1 - James F Wilson A1 - Daniel I Chasman A1 - Ilja M Nolte A1 - Tragante, Vinicius A1 - van der Laan, Sander W A1 - Perry, John R B A1 - Kong, Augustine A1 - Ahluwalia, Tarunveer S A1 - Albrecht, Eva A1 - Laura M Yerges-Armstrong A1 - Atzmon, Gil A1 - Auro, Kirsi A1 - Kristin L. Ayers A1 - Bakshi, Andrew A1 - Ben-Avraham, Danny A1 - Klaus Berger A1 - Bergman, Aviv A1 - Bertram, Lars A1 - Bielak, Lawrence F A1 - Bjornsdottir, Gyda A1 - Bonder, Marc Jan A1 - Broer, Linda A1 - Bui, Minh A1 - Barbieri, Caterina A1 - Cavadino, Alana A1 - Chavarro, Jorge E A1 - Turman, Constance A1 - Maria Pina Concas A1 - Cordell, Heather J A1 - Gail Davies A1 - Eibich, Peter A1 - Eriksson, Nicholas A1 - Tõnu Esko A1 - Eriksson, Joel A1 - Falahi, Fahimeh A1 - Felix, Janine F A1 - Mark Alan Fontana A1 - Lude L Franke A1 - Gandin, Ilaria A1 - Gaskins, Audrey J A1 - Gieger, Christian A1 - Gunderson, Erica P A1 - Guo, Xiuqing A1 - Caroline Hayward A1 - He, Chunyan A1 - Edith Hofer A1 - Huang, Hongyan A1 - Joshi, Peter K A1 - Kanoni, Stavroula A1 - Karlsson, Robert A1 - Kiechl, Stefan A1 - Kifley, Annette A1 - Kluttig, Alexander A1 - Kraft, Peter A1 - Lagou, Vasiliki A1 - Lecoeur, Cecile A1 - Lahti, Jari A1 - Li-Gao, Ruifang A1 - Penelope A Lind A1 - Tian Liu A1 - Makalic, Enes A1 - Mamasoula, Crysovalanto A1 - Lindsay K Matteson A1 - Mbarek, Hamdi A1 - McArdle, Patrick F A1 - McMahon, George A1 - Meddens, S Fleur W A1 - Mihailov, Evelin A1 - Michael B Miller A1 - Missmer, Stacey A A1 - Monnereau, Claire A1 - van der Most, Peter J A1 - Myhre, Ronny A1 - Michael A Nalls A1 - Nutile, Teresa A1 - Ioanna Panagiota Kalafati A1 - Porcu, Eleonora A1 - Prokopenko, Inga A1 - Rajan, Kumar B A1 - Rich-Edwards, Janet A1 - Cornelius A Rietveld A1 - Robino, Antonietta A1 - Rose, Lynda M A1 - Rueedi, Rico A1 - Ryan, Kathleen A A1 - Saba, Yasaman A1 - Schmidt, Daniel A1 - Jennifer A Smith A1 - Stolk, Lisette A1 - Streeten, Elizabeth A1 - Tönjes, Anke A1 - Thorleifsson, Gudmar A1 - Ulivi, Sheila A1 - Wedenoja, Juho A1 - Jürgen Wellmann A1 - Willeit, Peter A1 - Yao, Jie A1 - Yengo, Loic A1 - Jing Hua Zhao A1 - Wei Zhao A1 - Zhernakova, Daria V A1 - Amin, Najaf A1 - Andrews, Howard A1 - Balkau, Beverley A1 - Barzilai, Nir A1 - Bergmann, Sven A1 - Biino, Ginevra A1 - Bisgaard, Hans A1 - Bønnelykke, Klaus A1 - Dorret I Boomsma A1 - Buring, Julie E A1 - Campbell, Harry A1 - Cappellani, Stefania A1 - Ciullo, Marina A1 - Cox, Simon R A1 - Francesco Cucca A1 - Toniolo, Daniela A1 - Davey-Smith, George A1 - Ian J Deary A1 - George Dedoussis A1 - Deloukas, Panos A1 - Cornelia M van Duijn A1 - Eco J. C. de Geus A1 - Johan G Eriksson A1 - Jessica Faul A1 - Cinzia Felicita Sala A1 - Froguel, Philippe A1 - Paolo P. Gasparini A1 - Giorgia G Girotto A1 - Hans-Jörgen Grabe A1 - Greiser, Karin Halina A1 - Groenen, Patrick J F A1 - de Haan, Hugoline G A1 - Haerting, Johannes A1 - Tamara B Harris A1 - Andrew C Heath A1 - Heikkilä, Kauko A1 - Hofman, Albert A1 - Homuth, Georg A1 - Holliday, Elizabeth G A1 - John L Hopper A1 - Hyppönen, Elina A1 - Jacobsson, Bo A1 - Vincent Jaddoe A1 - Johannesson, Magnus A1 - Jugessur, Astanand A1 - Kähönen, Mika A1 - Kajantie, Eero A1 - Sharon L R Kardia A1 - Keavney, Bernard A1 - Kolcic, Ivana A1 - Koponen, Päivikki A1 - Kovacs, Peter A1 - Kronenberg, Florian A1 - Kutalik, Zoltán A1 - La Bianca, Martina A1 - Lachance, Genevieve A1 - Iacono, William G A1 - Lai, Sandra A1 - Lehtimäki, Terho A1 - David C Liewald A1 - Lindgren, Cecilia M A1 - Yongmei Liu A1 - Luben, Robert A1 - Lucht, Michael A1 - Luoto, Riitta A1 - Magnus, Per A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - McQuillan, Ruth A1 - Sarah E Medland A1 - Meisinger, Christa A1 - Mellström, Dan A1 - Andres Metspalu A1 - Traglia, Michela A1 - Lili Milani A1 - Mitchell, Paul A1 - Grant W Montgomery A1 - Dennis O Mook-Kanamori A1 - de Mutsert, Renée A1 - Nohr, Ellen A A1 - Ohlsson, Claes A1 - Olsen, Jørn A1 - Ong, Ken K A1 - Paternoster, Lavinia A1 - Pattie, Alison A1 - Brenda W J H Penninx A1 - Markus Perola A1 - Peyser, Patricia A A1 - Pirastu, Mario A1 - Polasek, Ozren A1 - Power, Chris A1 - Kaprio, Jaakko A1 - Raffel, Leslie J A1 - Katri Räikkönen A1 - Olli T Raitakari A1 - Ridker, Paul M A1 - Ring, Susan M A1 - Roll, Kathryn A1 - Rudan, Igor A1 - Ruggiero, Daniela A1 - Rujescu, Dan A1 - Veikko Salomaa A1 - Schlessinger, David A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Schupf, Nicole A1 - Johannes H Smit A1 - Sorice, Rossella A1 - Timothy Spector A1 - John M Starr A1 - Stöckl, Doris A1 - Strauch, Konstantin A1 - Stumvoll, Michael A1 - Swertz, Morris A A1 - Thorsteinsdottir, Unnur A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - Tung, Joyce Y A1 - André G Uitterlinden A1 - Vaccargiu, Simona A1 - Viikari, Jorma A1 - Vitart, Veronique A1 - Völzke, Henry A1 - Vollenweider, Peter A1 - Vuckovic, Dragana A1 - Waage, Johannes A1 - Wagner, Gert G A1 - Wang, Jie Jin A1 - Wareham, Nicholas J A1 - David R Weir A1 - Gonneke Willemsen A1 - Willeit, Johann A1 - Alan F Wright A1 - Krina T Zondervan A1 - Stefansson, Kari A1 - Krueger, Robert F A1 - Lee, James J A1 - Daniel J. Benjamin A1 - Cesarini, David A1 - Philipp D Koellinger A1 - den Hoed, Marcel A1 - Snieder, Harold A1 - Melinda C Mills AB -

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.

VL - 48 IS - 12 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27798627?dopt=Abstract ER -