Manuel Mattheisen

Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Hang Zhou, Yale School of Medicine, Yale University, Veterans Affairs Connecticut Healthcare System
  • ,
  • Julia M Sealock, Vanderbilt University Medical Center
  • ,
  • Sandra Sanchez-Roige, University of California San Diego
  • ,
  • Toni-Kim Clarke, Edinburgh University, Edinburgh
  • ,
  • Daniel F Levey, Yale School of Medicine, Yale University, Veterans Affairs Connecticut Healthcare System
  • ,
  • Zhongshan Cheng, Yale School of Medicine, Yale University, Veterans Affairs Connecticut Healthcare System
  • ,
  • Boyang Li, Yale School of Public Health
  • ,
  • Renato Polimanti, Yale School of Medicine, Yale University, Veterans Affairs Connecticut Healthcare System
  • ,
  • Rachel L Kember, University of Pennsylvania Perelman School of Medicine, Crescenz Veterans Affairs Medical Center
  • ,
  • Rachel Vickers Smith, University of Louisville School of Nursing
  • ,
  • Johan H Thygesen, University College London, London
  • ,
  • Marsha Y Morgan, University College London, London
  • ,
  • Stephen R Atkinson, Imperial College London
  • ,
  • Mark R Thursz, Imperial College London
  • ,
  • Mette Nyegaard
  • Manuel Mattheisen
  • Anders D Børglum
  • Emma C Johnson, Washington University School of Medicine, Yale School of Medicine
  • ,
  • Amy C Justice, Veterans Affairs Connecticut Healthcare System, Yale School of Medicine, Yale School of Public Health
  • ,
  • Abraham A Palmer, University of California San Diego
  • ,
  • Andrew McQuillin, University College London, London
  • ,
  • Lea K Davis, Vanderbilt University Medical Center
  • ,
  • Howard J Edenberg, Indiana University School of Medicine
  • ,
  • Arpana Agrawal, Washington University School of Medicine
  • ,
  • Henry R Kranzler, Crescenz Veterans Affairs Medical Center, University of Pennsylvania Perelman School of Medicine
  • ,
  • Joel Gelernter, Yale School of Medicine, Yale University, Veterans Affairs Connecticut Healthcare System

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.

Original languageEnglish
JournalNature Neuroscience
Volume23
Issue7
Pages (from-to)809-818
Number of pages10
ISSN1097-6256
DOIs
Publication statusPublished - Jul 2020

    Research areas

  • ASSOCIATION, BIOBANK, DEPENDENCE, DISORDER, GWAS, HERITABILITY, LD SCORE REGRESSION, LOCI, MENDELIAN RANDOMIZATION, RISK

See relations at Aarhus University Citationformats

ID: 189537841