TY - JOUR
T1 - Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders
AU - 23andMe Research Team
AU - Walters, Raymond K.
AU - Polimanti, Renato
AU - Johnson, Emma C.
AU - McClintick, Jeanette N.
AU - Adams, Mark J.
AU - Adkins, Amy E.
AU - Aliev, Fazil
AU - Bacanu, Silviu Alin
AU - Batzler, Anthony
AU - Bertelsen, Sarah
AU - Biernacka, Joanna M.
AU - Bigdeli, Tim B.
AU - Chen, Li Shiun
AU - Clarke, Toni Kim
AU - Chou, Yi Ling
AU - Degenhardt, Franziska
AU - Docherty, Anna R.
AU - Edwards, Alexis C.
AU - Fontanillas, Pierre
AU - Foo, Jerome C.
AU - Fox, Louis
AU - Frank, Josef
AU - Giegling, Ina
AU - Gordon, Scott
AU - Hack, Laura M.
AU - Hartmann, Annette M.
AU - Hartz, Sarah M.
AU - Heilmann-Heimbach, Stefanie
AU - Herms, Stefan
AU - Hodgkinson, Colin
AU - Hoffmann, Per
AU - Jan Hottenga, Jouke
AU - Kennedy, Martin A.
AU - Alanne-Kinnunen, Mervi
AU - Konte, Bettina
AU - Lahti, Jari
AU - Lahti-Pulkkinen, Marius
AU - Lai, Dongbing
AU - Ligthart, Lannie
AU - Loukola, Anu
AU - Saccone, Nancy L.
AU - Culverhouse, Robert C.
AU - Bierut, Laura J.
AU - Bucholz, Kathleen K.
AU - Grucza, Richard A.
AU - Heath, Andrew C.
AU - Madden, Pamela A.F.
AU - Nelson, Elliot C.
AU - Rice, John P.
AU - Agrawal, Arpana
N1 - Publisher Copyright:
© 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case–control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10–13) and African ancestries (rs2066702; P = 2.2 × 10–9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit–hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.
AB - Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case–control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10–13) and African ancestries (rs2066702; P = 2.2 × 10–9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit–hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.
UR - http://www.scopus.com/inward/record.url?scp=85057260886&partnerID=8YFLogxK
U2 - 10.1038/s41593-018-0275-1
DO - 10.1038/s41593-018-0275-1
M3 - Article
C2 - 30482948
AN - SCOPUS:85057260886
SN - 1097-6256
VL - 21
SP - 1656
EP - 1669
JO - Nature neuroscience
JF - Nature neuroscience
IS - 12
ER -