@article{4d0ff18875c44109a070607bf41d4958,
title = "The etiology of DSM-5 alcohol use disorder: Evidence of shared and non-shared additive genetic effects",
abstract = "Background: Alcoholism is a multifactorial disorder influenced by multiple gene loci, each with small effect. Studies suggest shared genetic influences across DSM-IV alcohol dependence symptoms, but shared effects across DSM-5 alcohol use disorder remains unknown. We aimed to test the assumption of genetic homogeneity across the 11 criteria of DSM-5 alcohol use disorder (AUD). Methods: Data from 2596 alcohol using individuals of European ancestry from the Study of Addiction: Genetics and Environment were used to examine the genomewide SNP-heritability (h2SNP) and SNP-covariance (rGSNP) between 11 DSM-5 AUD symptoms. Phenotypic relationships between symptoms were examined to confirm an underlying liability of AUD and the SNP-heritability of the observed latent trait and the co-heritabilityamong AUD symptoms was assessed using Genomic-Relatedness-Matrix-Restricted-Maximum-Likelihood. Genetic covariance among symptoms was examined using factor analysis. Results: Phenotypic relationships confirmed a unidimensional underlying liability to AUD. Factor and parallel analyses of the observed genetic variance/covariance provided evidence of genetic homogeneity. Additive genetic effects on DSM-5 AUD symptoms varied from 0.10 to 0.37 and largely overlapped (rG-SNP across symptoms ranged from 0.49 - 0.92). The additive genetic effect on the DSM-5 AUD factor was 0.36, 0.14 for DSM-5 AUD diagnosis, and was 0.22 for DSM-5 AUD severity. Conclusions: Common genetic variants influence DSM-5 AUD symptoms. Despite evidence for a common AUD factor, the evidence of only partially overlapping genetic effects across AUD symptoms further substantiates the need to simultaneously model common and symptom-specific genetic effects in molecular genetic studies in order to best characterize the genetic liability.",
keywords = "Alcohol use disorder, Ancestry, DSM-5, European, Genetics, Heritability",
author = "Palmer, {Rohan H.C.} and Brick, {Leslie A.} and Chou, {Yi Ling} and Arpana Agrawal and McGeary, {John E.} and Heath, {Andrew C.} and Laura Bierut and Keller, {Matthew C.} and Eric Johnson and Hartz, {Sarah M.} and Schuckit, {Marc A.} and Knopik, {Valerie S.}",
note = "Funding Information: This body of work was supported by research grants from the National Institute on Alcohol Abuse and Alcoholism ( K01AA021113 awarded to Rohan Palmer, R01AA02559 awarded to John McGeary and P60AA11998 awarded to Andrew Heath, and K02DA032573 and R21AA021235 awarded to Arpana Agrawal) and the National Institute on Mental Health ( R01MH100141 awarded to Matthew Keller and R56MH108650 awarded to John McGeary). Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] ( U01 HG004422 ). SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center ( U01 HG004446 ). Assistance with data cleaning was provided by the National Center for Biotechnology Information . Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401 ), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392 ), and the Family Study of Cocaine Dependence (FSCD; R01 DA013423 , R01 DA019963 ). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI ( U01HG004438 ), the National Institute on Alcohol Abuse and Alcoholism , the National Institute on Drug Abuse , and the NIH contract {"}High throughput genotyping for studying the genetic contributions to human disease{"} (HHSN268200782096C). The views expressed in this article do not necessarily reflect the position or policy of the Department of Veterans Affairs. Funding Information: We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting-Kai Li, P. Michael Conneally, Raymond Crowe, and Wendy Reich, for their critical contributions. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). Publisher Copyright: {\textcopyright} 2019",
year = "2019",
month = aug,
day = "1",
doi = "10.1016/j.drugalcdep.2018.12.034",
language = "English",
volume = "201",
pages = "147--154",
journal = "Drug and Alcohol Dependence",
issn = "0376-8716",
}