Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

23andMe Research Team

doi:10.1038/s41593-018-0275-1

Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

23andMe Research Team

Research output: Contribution to journal › Article › peer-review

357 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1656-1669
Number of pages	14
Journal	Nature Neuroscience
Volume	21
Issue number	12
Early online date	26 Nov 2018
DOIs	https://doi.org/10.1038/s41593-018-0275-1
Publication status	Published - 31 Dec 2018

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@article{4668e3060a8e455e896e02afa714fb2d,

title = "Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders",

abstract = "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.",

author = "Walters, {Raymond K} and Renato Polimanti and Johnson, {Emma C} and McClintick, {Jeanette N} and Adams, {Mark J} and Adkins, {Amy E} and Fazil Aliev and Silviu-Alin Bacanu and Anthony Batzler and Sarah Bertelsen and Biernacka, {Joanna M} and Bigdeli, {Tim B} and Li-Shiun Chen and Toni-Kim Clarke and Yi-Ling Chou and Franziska Degenhardt and Docherty, {Anna R} and Edwards, {Alexis C} and Pierre Fontanillas and Foo, {Jerome C} and Louis Fox and Josef Frank and Ina Giegling and Scott Gordon and Hack, {Laura M} and Hartmann, {Annette M} and Hartz, {Sarah M} and Stefanie Heilmann-Heimbach and Stefan Herms and Colin Hodgkinson and Per Hoffmann and {Jan Hottenga}, Jouke and Kennedy, {Martin A} and Mervi Alanne-Kinnunen and Bettina Konte and Jari Lahti and Marius Lahti-Pulkkinen and Dongbing Lai and Lannie Ligthart and Anu Loukola and Maher, {Brion S} and Hamdi Mbarek and McIntosh, {Andrew M} and McQueen, {Matthew B} and Meyers, {Jacquelyn L} and Yuri Milaneschi and Teemu Palviainen and Pearson, {John F} and Peterson, {Roseann E} and Murray, {Alison D} and {23andMe Research Team}",

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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 - Maher, Brion S

AU - Mbarek, Hamdi

AU - McIntosh, Andrew M

AU - McQueen, Matthew B

AU - Meyers, Jacquelyn L

AU - Milaneschi, Yuri

AU - Palviainen, Teemu

AU - Pearson, John F

AU - Peterson, Roseann E

AU - Murray, Alison D

AU - 23andMe Research Team

PY - 2018/12/31

Y1 - 2018/12/31

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.

U2 - 10.1038/s41593-018-0275-1

DO - 10.1038/s41593-018-0275-1

M3 - Article

C2 - 30482948

SN - 1097-6256

VL - 21

SP - 1656

EP - 1669

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 12

ER -

Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

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