TY  - JOUR
AV  - public
KW  - Addiction
KW  -  Genome-wide association studies
N2  - Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies have identified PAU risk genes, the genetic architecture of this trait is not fully understood. We conducted a proxy-phenotype meta-analysis of PAU, combining alcohol use disorder and problematic drinking, in 435,563?European-ancestry individuals. We identified 29?independent risk variants, 19 of them novel. PAU was genetically correlated with 138?phenotypes, including substance use and psychiatric traits. Phenome-wide polygenic risk score analysis in an independent biobank sample (BioVU, n?=?67,589) confirmed the genetic correlations between PAU and substance use and psychiatric disorders. Genetic heritability of PAU was enriched in brain and in conserved and regulatory genomic regions. Mendelian randomization suggested causal effects on liability to PAU of substance use, psychiatric status, risk-taking behavior and cognitive performance. In summary, this large PAU meta-analysis identified novel risk loci and revealed genetic relationships with numerous other traits.
ID  - discovery10099547
SP  - 809
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
UR  - http://dx.doi.org/10.1038/s41593-020-0643-5
EP  - 818
A1  - Zhou, H
A1  - Sealock, JM
A1  - Sanchez-Roige, S
A1  - Clarke, T-K
A1  - Levey, DF
A1  - Cheng, Z
A1  - Li, B
A1  - Polimanti, R
A1  - Kember, RL
A1  - Smith, RV
A1  - Thygesen, JH
A1  - Morgan, MY
A1  - Atkinson, SR
A1  - Thursz, MR
A1  - Nyegaard, M
A1  - Mattheisen, M
A1  - Børglum, AD
A1  - Johnson, EC
A1  - Justice, AC
A1  - Palmer, AA
A1  - McQuillin, A
A1  - Davis, LK
A1  - Edenberg, HJ
A1  - Agrawal, A
A1  - Kranzler, HR
A1  - Gelernter, J
Y1  - 2020/07//
TI  - Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits
JF  - Nature Neuroscience
VL  - 23
SN  - 1546-1726
ER  -