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Twin Res Hum Genet. 2015 Aug;18(4):335-47. doi: 10.1017/thg.2015.36. Epub 2015 Jun 17.

Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood.

Author information

1
Center for Biomarker Research and Personalized Medicine,Virginia Commonwealth University,School of Pharmacy,Richmond,Virginia,USA.
2
Department of Psychiatry,Duke University Medical Center,Durham,North Carolina,USA.
3
Department of Pathology,University of Otago,Christchurch,New Zealand.
4
Division of Epidemiology,Services and Prevention Research,National Institute on Drug Abuse,Bethesda,Maryland,USA.
5
Virginia Institute for Psychiatric and Behavioral Genetics,Virginia Commonwealth University,Richmond,Virginia,USA.
6
Thurston Arthritis Research Center,University of North Carolina at Chapel Hill,Chapel Hill,North Carolina,USA.
7
Center for Medicine,Health and Society,Vanderbilt University,Nashville,Tennessee,USA.
8
Department of Psychological Medicine,University of Otago,Christchurch,New Zealand.
9
Departments of Genetics and Psychiatry,University of North Carolina at Chapel Hill,Chapel Hill,North Carolina,USA.

Abstract

The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N=2,126, obs=12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR<0.1) and six others met our 'suggestive' criterion (FDR<0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.

KEYWORDS:

GABA; SLC6A1; alcohol; developmental trajectory; genome-wide; longitudinal

PMID:
26081443
PMCID:
PMC4762598
DOI:
10.1017/thg.2015.36
[Indexed for MEDLINE]
Free PMC Article

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