Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated (|r^g| ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.
Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences / Linner Richard Karlsson; Biroli P; Kong Edward; Meddens Fleur W.; Wedow Robbee; Fontana Mark Alan; Lebreton Mael; Tino Stephen P.; Abdellaoui Abdel; Hammerschlag Anke R.; Nivard Michel G.; Okbay Aysu; Rietveld Cornelius A.; Timshel Pascal N.; Trzaskowski Maciej; de Vlaming Ronald; Zund Christian L.; Bao Yanchun; Buzdugan Laura; Caplin Ann H.; Chen Chia-Yen; Eibich Peter; Fontanillas Pierre; Gonzalez Juan R.; Joshi Peter K.; Karhunen Ville; Kleinman Aaron; Levin Remy Z.; Lill Christina M.; Meddens Gerardus A.; Muntane Gerard; Sanchez-Roige Sandra; van Rooij Frank J.; Taskesen Erdogan; Wu Yang; Zhang Futao; Agee Michelle; Alipanahi Babak; Bell Robert K.; Bryc Katarzyna; Elson Sarah L.; Furlotte Nicholas A.; Huber Karen E.; Litterman Nadia K.; McCreight Jennifer C.; McIntyre Matthew H.; Mountain Joanna L.; Northover Carrie A. M.; Pitts Steven J.; Sathirapongsasuti J. Fah; Sazonova Olga V.; Shelton Janie F.; Shringarpure Suyash; Tian Chao; Tung Joyce Y.; Vacic Vladimir; Wilson Catherine H.; Agbessi Mawusse; Ahsan Habibul; Alves Isabel; Andiappan Anand; Awadalla Philip; Battle Alexis; Beutner Frank; Bonder Marc Jan; Boomsma Dorret I.; Christiansen Mark; Claringbould Annique; Deelen Patrick; Esko Tonu; Fave Marie-Julie; Franke Lude; Frayling Timothy; Gharib Sina A.; Gibson Gregory; Heijmans Bastiaan; Hemani Gibran; Jansen Rick; Kahonen Mika; Kalnapenkis Anette; Kasela Silva; Kettunen Johannes; Kim Yungil; Kirsten Holger; Kovacs Peter; Krohn Knut; Kronberg-Guzman Jaanika; Kukushkina Viktorija; Kutalik Zoltan; Lee Bernett; Lehtimaki Terho; Loeffler Markus; Marigorta Urko M.; Metspalu Andres; Milani Lili; Montgomery Grant W.; Mueller-Nurasyid Martina; Nauck Matthias; Penninx Brenda; Perola Markus; Pervjakova Natalia; Pierce Brandon; Powell Joseph; Prokisch Holger; Psaty Bruce M.; Raitakari Olli; Ring Susan; Ripatti Samuli; Rotzchke Olaf; Rueger Sina; Saha Ashis; Scholz Markus; Schramm Katharina; Seppala Ilkka; Stumvoll Michael; Sullivan Patrick; Hoen Peter-Bramt; Teumer Alexander; Thiery Joachim; Tong Lin; Tonjes Anke; van Dongen Jenny; van Meurs Joyce; Verlouw Joost; Visscher Peter M.; Voelker Uwe; Vosa Urmo; Westra Harm-Jan; Yaghootkar Hanieh; Yang Jian; Zeng Biao; Lee James J.; Pers Tune H.; Turley Patrick; Chen Guo-Bo; Emilsson Valur; Oskarsson Sven; Pickrell Joseph K.; Thom Kevin; Timshel Pascal; Ahluwalia Tarunveer S.; Bacelis Jonas; Baumbach Clemens; Bjornsdottir Gyda; Brandsma Johannes H.; Concas Maria Pina; Derringer Jaime; Furlotte Nicholas A.; Galesloot Tessel E.; Girotto Giorgia; Gupta Richa; Hall Leanne M.; Harris Sarah E.; Hofer Edith; Horikoshi Momoko; Huffman Jennifer E.; Kaasik Kadri; Kalafati Ioanna P.; Kong Augustine; Lahti Jari; van der Lee Sven J.; de Leeuw Christiaan; Lind Penelope A.; Lindgren Karl-Oskar; Liu Tian; Mangino Massimo; Marten Jonathan; Mihailov Evelin; Miller Michael B.; van der Most Peter J.; Oldmeadow Christopher; Payton Antony; Pervjakova Natalia; Peyrot Wouter J.; Qian Yong; Raitakari Olli; Rueedi Rico; Salvi Erika; Schmidt Boerge; Schraut Katharina E.; Shi Jianxin; Smith Albert V.; Poot Raymond A.; St Pourcain Beate; Teumer Alexander; Thorleifsson Gudmar; Verweij Niek; Vuckovic Dragana; Wellmann Juergen; Westra Harm-Jan; Yang Jingyun; Zhao Wei; Zhu Zhihong; Alizadeh Behrooz Z.; Amin Najaf; Bakshi Andrew; Baumeister Sebastian E.; Biino Ginevra; Bonnelykke Klaus; Boyle Patricia A.; Campbell Harry; Cappuccio Francesco P.; Davies Gail; De Neve Jan-Emmanuel; Deloukas Panos; Demuth Ilja; Ding Jun; Eibich Peter; Eisele Lewin; Eklund Niina; Evans David M.; Faul Jessica D.; Feitosa Mary F.; Forstner Andreas J.; Gandin Ilaria; Gunnarsson Bjarni; Halldorsson Bjarni V.; Harris Tamara B.; Heath Andrew C.; Hocking Lynne J.; Holliday Elizabeth G.; Homuth Georg; Horan Michael A.; Hottenga Jouke-Jan; de Jager Philip L.; Jugessur Astanand; Kaakinen Marika A.; Kahonen Mika; Kanoni Stavroula; Keltigangas-Jarvinen Liisa; Kiemeney Lambertus A. L. M.; Kolcic Ivana; Koskinen Seppo; Kraja Aldi T.; Kroh Martin; Kutalik Zoltan; Latvala Antti; Launer Lenore J.; Lebreton Mael P.; Levinson Douglas F.; Lichtenstein Paul; Lichtner Peter; Liewald David C. M.; Loukola Anu; Madden Pamela A.; Magi Reedik; Maki-Opas Tomi; Marioni Riccardo E.; Marques-Vidal Pedro; McMahon George; Meisinger Christa; Meitinger Thomas; Milaneschi Yusplitri; Milani Lili; Montgomery Grant W.; Myhre Ronny; Nelson Christopher P.; Nyholt Dale R.; Ollier William E. R.; Palotie Aarno; Paternoster Lavinia; Pedersen Nancy L.; Petrovic Katja E.; Porteous David J.; Raikkonen Katri; Ring Susan M.; Robino Antonietta; Rostapshova Olga; Rudan Igor; Rustichini Aldo; Salomaa Veikko; Sanders Alan R.; Sarin Antti-Pekka; Schmidt Helena; Scott Rodney J.; Smith Blair H.; Smith Jennifer A.; Staessen Jan A.; Steinhagen-Thiessen Elisabeth; Strauch Konstantin; Terracciano Antonio; Tobin Martin D.; Ulivi Sheila; Vaccargiu Simona; Quaye Lydia; Venturini Cristina; Vinkhuyzen Anna A. E.; Voelker Uwe; Voelzke Henry; Vonk Judith M.; Vozzi Diego; Waage Johannes; Ware Erin B.; Willemsen Gonneke; Attia John R.; Bennett David A.; Berger Klaus; Bertram Lars; Bisgaard Hans; Boomsma Dorret I.; Borecki Ingrid B.; Bultmann Ute; Chabris Christopher F.; Cucca Francesco; Cusi Daniele; Deary J.; Dedoussis George V.; van Duijn Cornelia M.; Eriksson Johan G.; Franke Barbara; Franke Lude; Gasparini Paolo; Gejman Pablo V.; Gieger Christian; Grabe Hans-Joergen; Gratten Jacob; Gudnason Vilmundur; van der Harst Pim; Hayward Caroline; Hinds David A.; Hoffmann Wolfgang; Hypponen Elina; Iacono William G.; Jacobsson Bo; Jarvelin Marjo-Riitta; Jockel Karl-Heinz; Kaprio Jaakko; Kardia Sharon L. R.; Lehtimaki Terho; Lehrer Steven F.; Magnusson Patrik K. E.; Martin Nicholas G.; McGue Matt; Metspalu Andres; Pendleton Neil; Penninx Brenda; Perola Markus; Pirastu Nicola; Pirastu Mario; Polasek Ozren; Posthuma Danielle; Power Christine; Province Michael A.; Samani Nilesh J.; Schlessinger David; Schmidt Reinhold; Sorensen Thorkild I. A.; Spector Tim D.; Stefansson Kari; Thorsteinsdottir Unnur; Thurik A. Roy; Timpson Nicholas J.; Tiemeier Henning; Tung Joyce Y.; Uitterlinden Andre G.; Vitart Veronique; Vollenweider Peter; Weir David R.; Wilson James F.; Wright Alan F.; Conley Dalton C.; Krueger Robert F.; Smith George Davey; Laibson David I.; Medland Sarah E.; Yang Jian; Johannesson Magnus; Visscher Peter M.; Esko Tonu; Koellinger Philipp D.; Cesarini David; Benjamin Daniel J.; Auton Adam; Boardman Jason D.; Clark David W.; Conlin Andrew; Dolan Conor C.; Fischbacher Urs; Groenen Patrick J. F.; Harris Kathleen Mullan; Hasler Gregor; Hofman Albert; Ikram Mohammad A.; Jain Sonia; Karlsson Robert; Kessler Ronald C.; Kooyman Maarten; MacKillop James; Mannikko Minna; Morcillo-Suarez Carlos; McQueen Matthew B.; Schmidt Klaus M.; Smart Melissa C.; Sutter Matthias; Thurik A. Roy; Uitterlinden Andre G.; White Jon; de Wit Harriet; Yang Jian; Bertram Lars; Boomsma Dorret I.; Esko Tonu; Fehr Ernst; Hinds David A.; Johannesson Magnus; Kumari Meena; Laibson David; Magnusson Patrik K. E.; Meyer Michelle N.; Navarro Arcadi; Palmer Abraham A.; Pers Tune H.; Posthuma Danielle; Schunk Daniel; Stein Murray B.; Svento Rauli; Tiemeier Henning; Timmers Paul R. H. J.; Turley Patrick; Ursano Robert J.; Wagner Gert G.; Wilson James F.; Gratten Jacob; Lee James J.; Cesarini David; Benjamin Daniel J.; Koellinger Philipp D.; Beauchamp Jonathan P.. - In: NATURE GENETICS. - ISSN 1061-4036. - ELETTRONICO. - 51:2(2019), pp. 245-257. [10.1038/s41588-018-0309-3]
Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
Biroli P;
2019
Abstract
Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated (|r^g| ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
