title: The Rate of Change in Alcohol Misuse Across Adolescence is Heritable.
abstract: Alcohol use typically begins during adolescence and escalates into young adulthood. This represents an important period for the establishment of alcohol use and misuse patterns, which can have psychosocial and medical consequences. Although changes in alcohol use during this time have been phenotypically characterized, their genetic nature is poorly understood.
  
  
  
  Participants of the Avon Longitudinal Study of Parents and Children completed the Alcohol Use Disorders Identification Test (AUDIT) 4 times from age 16 to 20. We used Mplus to construct a growth model characterizing changes in AUDIT scores across time (N = 4,545, where data were available for at least 2 time points). The slope of the model was used as the phenotype in a genomewide association study (N = 3,380), followed by secondary genetic analyses.
  
  
  
  No individual marker met genomewide significance criteria. Top markers mapped to biologically plausible candidate genes. The slope term was moderately heritable (h2SNP= 0.26, p = 0.009), and replication attempts using a meta-analysis of independent samples provided support for implicated variants at the aggregate level. Nominally significant (p < 0.00001) markers mapped to putatively active genomic regions in brain tissue more frequently than expected by chance.
  
  
  
  These results build on prior studies by demonstrating that common genetic variation impacts alcohol misuse trajectories. Influential loci map to genes that merit additional research, as well as to intergenic regions with regulatory functions in the central nervous system. These findings underscore the complex biological nature of alcohol misuse across development.
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Alexis C
authors.identifier: 0000-0002-4006-9710
authors.initials: AC
authors.lastname: Edwards
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Jon
authors.initials: J
authors.lastname: Heron
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.|Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, Richmond, Virginia.|Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia.|Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vladimirov
authors.affiliation: Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Wolen
authors.affiliation: Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Adkins
authors.affiliation: Department of African-American Studies, Virginia Commonwealth University, Richmond, Virginia.|Faculty of Business, Karabuk University, Karabuk, Turkey.
authors.forename: Fazil
authors.initials: F
authors.lastname: Aliev
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hickman
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
mesh_terms: D000293:Adolescent; D000428:Alcohol Drinking / Q000235:genetics* / Q000639:trends*; D000437:Alcoholism / Q000175:diagnosis* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods / Q000639:trends*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D055815:Young Adult
keywords: 
  ALSPAC
  ; Alcohol Problems; Genetic Influences; Heritability; Longitudinal Model