A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
Tekijät: Linner RK, Biroli P, Kong E, Meddens FW, Wedow R, Fontana MA, Lebreton M, Tino SP, Abdellaoui A, Hammerschlag AR, Nivard MG, Okbay A, Rietveld CA, Timshel PN, Trzaskowski M, Vlaming R, Zund CL, Bao YC, Buzdugan L, Caplin AH, Chen CY, Eibich P, Fontanillas P, Gonzalez JR, Joshi PK, Karhunen V, Kleinman A, Levin RZ, Lill CM, Meddens GA, Muntane G, Sanchez-Roige S, Rooij FJ, Taskesen E, Wu Y, Zhang FT, Agee M, Alipanahi B, Bell RK, Bryc K, Elson SL, Furlotte NA, Huber KE, Litterman NK, McCreight JC, McIntyre MH, Mountain JL, Northover CAM, Pitts SJ, Sathirapongsasuti JF, Sazonova OV, Shelton JF, Shringarpure S, Tian C, Tung JY, Vacic V, Wilson CH, Agbessi M, Ahsan H, Alves I, Andiappan A, Awadalla P, Battle A, Beutner F, Bonder MJ, Boomsma DI, Christiansen M, Claringbould A, Deelen P, Esko T, Fave MJ, Franke L, Frayling T, Gharib SA, Gibson G, Heijmans B, Hemani G, Jansen R, Kahonen M, Kalnapenkis A, Kasela S, Kettunen J, Kim Y, Kirsten H, Kovacs P, Krohn K, Kronberg-Guzman J, Kukushkina V, Kutalik Z, Lee B, Lehtimaki T, Loeffler M, Marigorta UM, Metspalu A, Milani L, Montgomery GW, Mueller-Nurasyid M, Nauck M, Penninx B, Perola M, Pervjakova N, Pierce B, Powell J, Prokisch H, Psaty BM, Raitakari O, Ring S, Ripatti S, Rotzchke O, Rueger S, Saha A, Scholz M, Schramm K, Seppala I, Stumvoll M, Sullivan P, Hoen PB, Teumer A, Thiery J, Tong L, Tonjes A, van Dongen J, van Meurs J, Verlouw J, Visscher PM, Volker U, Vosa U, Westra HJ, Yaghootkar H, Yang J, Zeng B, Lee JJ, Pers TH, Turley P, Chen GB, Emilsson V, Oskarsson S, Pickrell JK, Thom K, Timshel P, Ahluwalia TS, Bacelis J, Baumbach C, Bjornsdottir G, Brandsma JH, Concas MP, Derringer J, Furlotte NA, Galesloot TE, Girotto G, Gupta R, Hall LM, Harris SE, Hofer E, Horikoshi M, Huffman JE, Kaasik K, Kalafati IP, Kong A, Lahti J, Lee SJD, Leeuw C, Lind PA, Lindgren KO, Liu T, Mangino M, Marten J, Mihailov E, Miller MB, Most PJD, Oldmeadow C, Payton A, Pervjakova N, Peyrot WJ, Qian Y, Raitakari O, Rueedi R, Salvi E, Schmidt B, Schraut KE, Shi J, Smith AV, Poot RA, Pourcain B, Teumer A, Thorleifsson G, Verweij N, Vuckovic D, Wellmann J, Westra HJ, Yang JY, Zhao W, Zhu ZH, Alizadeh BZ, Amin N, Bakshi A, Baumeister SE, Biino G, Bonnelykke K, Boyle PA, Campbell H, Cappuccio FP, Davies G, De Neve JE, Deloukas P, Demuth I, Ding J, Eibich P, Eisele L, Eklund N, Evans DM, Faul JD, Feitosa MF, Forstner AJ, Gandin I, Gunnarsson B, Halldorsson BV, Harris TB, Heath AC, Hocking LJ, Holliday EG, Homuth G, Horan MA, Hottenga JJ, Jager PL, Jugessur A, Kaakinen MA, Kahonen M, Kanoni S, Keltigangas-Jarvinen L, Kiemeney LALM, Kolcic I, Koskinen S, Kraja AT, Kroh M, Kutalik Z, Latvala A, Launer LJ, Lebreton MP, Levinson DF, Lichtenstein P, Lichtner P, Liewald DCM, Loukola A, Madden PA, Magi R, Maki-Opas T, Marioni RE, Marques-Vidal P, McMahon G, Meisinger C, Meitinger T, Milaneschi Y, Milani L, Montgomery GW, Myhre R, Nelson CP, Nyholt DR, Ollier WER, Palotie A, Paternoster L, Pedersen NL, Petrovic KE, Porteous DJ, Raikkonen K, Ring SM, Robino A, Rostapshova O, Rudan I, Rustichini A, Salomaa V, Sanders AR, Sarin AP, Schmidt H, Scott RJ, Smith BH, Smith JA, Staessen JA, Steinhagen-Thiessen E, Strauch K, Terracciano A, Tobin MD, Ulivi S, Vaccargiu S, Quaye L, Venturini C, Vinkhuyzen AAE, Volker U, Voelzke H, Vonk JM, Vozzi D, Waage J, Ware EB, Willemsen G, Attia JR, Bennett DA, Berger K, Bertram L, Bisgaard H, Boomsma DI, Borecki IB, Bultmann U, Chabris CF, Cucca F, Cusi D, Deary J, Dedoussis GV, Duijn CM, Eriksson JG, Franke B, Franke L, Gasparini P, Gejman PV, Gieger C, Grabe HJ, Gratten J, Gudnason V, Harst PD, Hayward C, Hinds DA, Hoffmann W, Hypponen E, Iacono WG, Jacobsson B, Jarvelin MR, Jockel KH, Kaprio J, Kardia SLR, Lehtimaki T, Lehrer SF, Magnusson PKE, Martin NG, Mcgue M, Metspalu A, Pendleton N, Penninx B, Perola M, Pirastu N, Pirastu M, Polasek O, Posthuma D, Power C, Province MA, Samani NJ, Schlessinger D, Schmidt R, Sorensen TIA, Spector TD, Stefansson K, Thorsteinsdottir U, Thurik AR, Timpson NJ, Tiemeier H, Tung JY, Uitterlinden AG, Vitart V, Vollenweider P, Weir DR, Wilson JF, Wright AF, Conley DC, Krueger RF, Smith GD, Laibson DI, Medland SE, Yang J, Johannesson M, Visscher PM, Esko T, Koellinger PD, Cesarini D, Benjamin DJ, Auton A, Boardman JD, Clark DW, Conlin A, Dolan CC, Fischbacher U, Groenen PJF, Harris KM, Hasler G, Hofman A, Ikram MA, Jain S, Karlsson R, Kessler RC, Kooyman M, MacKillop J, Mannikko M, Morcillo-Suarez C, McQueen MB, Schmidt KM, Smart MC, Sutter M, Thurik AR, Uitterlinden AG, White J, de Wit H, Yang J, Bertram L, Boomsma DI, Esko T, Fehr E, Hinds DA, Johannesson M, Kumari M, Laibson D, Magnusson PKE, Meyer MN, Navarro A, Palmer AA, Pers TH, Posthuma D, Schunk D, Stein MB, Svento R, Tiemeier H, Timmers PRHJ, Turley P, Ursano RJ, Wagner GG, Wilson JF, Gratten J, Lee JJ, Cesarini D, Benjamin DJ, Koellinger PD, Beauchamp JP, Cesarini D, Lee JJ, Koellinger PD, Benjamin DJ, Beauchamp JP, Gratten J
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2019
Journal: Nature Genetics
Tietokannassa oleva lehden nimi: NATURE GENETICS
Lehden akronyymi: NAT GENET
Vuosikerta: 51
Numero: 2
Aloitussivu: 245
Lopetussivu: 257
Sivujen määrä: 16
ISSN: 1061-4036
eISSN: 1546-1718
DOI: https://doi.org/10.1038/s41588-018-0309-3
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 (vertical bar(r) over cap (g)vertical bar similar to 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.