@article{a7700785e78c459b867f3c269c10778a,
title = "Post-GWAS analysis of six substance use traits improves the identification and functional interpretation of genetic risk loci",
abstract = "Background: Little is known about the functional mechanisms through which genetic loci associated with substance use traits ascertain their effect. This study aims to identify and functionally annotate loci associated with substance use traits based on their role in genetic regulation of gene expression. Methods: We evaluated expression Quantitative Trait Loci (eQTLs) from 13 brain regions and whole blood of the Genotype-Tissue Expression (GTEx) database, and from whole blood of the Depression Genes and Networks (DGN) database. The role of single eQTLs was examined for six substance use traits: alcohol consumption (N = 537,349), cigarettes per day (CPD; N = 263,954), former vs. current smoker (N = 312,821), age of smoking initiation (N = 262,990), ever smoker (N = 632,802), and cocaine dependence (N = 4,769). Subsequently, we conducted a gene level analysis of gene expression on these substance use traits using S-PrediXcan. Results: Using an FDR-adjusted p-value <0.05 we found 2,976 novel candidate genetic loci for substance use traits, and identified genes and tissues through which these loci potentially exert their effects. Using S-PrediXcan, we identified significantly associated genes for all substance traits. Discussion: Annotating genes based on transcriptomic regulation improves the identification and functional characterization of candidate loci and genes for substance use traits.",
keywords = "Addiction, eQTLs, Functional annotation, GTEx, Substance use, S-PrediXcan, ANTERIOR CINGULATE CORTEX, FAMILY-HISTORY, ALCOHOL DEPENDENCE, NUCLEUS-ACCUMBENS, EXPRESSION, COCAINE, TRANSCRIPTION, ASSOCIATION, 17Q21.31",
author = "{Int Cannabis Consortium} and Marees, {Andries T.} and Gamazon, {Eric R.} and Zachary Gerring and Florence Vorspan and Josh Fingal and {van den Brink}, Wim and Smit, {Dirk J. A.} and Verweij, {Karin J. H.} and Kranzler, {Henry R.} and Richard Sherva and Lindsay Farrer and Sven Stringer and Minica, {Camelia C.} and Hamdi Mbarek and Manon Bernard and Jaime Derringer and {van Eijk}, {Kristel R.} and Isen, {Joshua D.} and Anu Loukola and Maciejewski, {Dominique F.} and Evelin Mihailov and {van der Most}, {Peter J.} and Cristina Sanchez-Mora and Leonie Roos and Raymond Walters and Ware, {Jennifer J.} and Abdel Abdellaoui and Bigdeli, {Timothy B.} and Branje, {Susan J. T.} and Brown, {Sandra A.} and Marcel Bruinenberg and Miguel Casas and Tonu Esko and Iris Garcia-Martinez and Gordon, {Scott D.} and Harris, {Juliette M.} and Hartman, {Catharina A.} and Henders, {Anjali K.} and Heath, {Andrew C.} and Hickie, {Ian B.} and Matthew Hickman and Hopfer, {Christian J.} and Hottenga, {Jouke Jan} and Huizink, {Anja C.} and Irons, {Daniel E.} and Kahn, {Rene S.} and Nolte, {Ilja M.} and Oldehinkel, {Albertine J.} and Boks, {Marco P.} and Harold Snieder",
year = "2020",
month = jan,
day = "1",
doi = "10.1016/j.drugalcdep.2019.107703",
language = "English",
volume = "206",
journal = "Drug and Alcohol Dependence",
issn = "0376-8716",
publisher = "ELSEVIER IRELAND LTD",
}