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

Publication ,  Journal Article
Adkins, DE; Clark, SL; Copeland, WE; Kennedy, M; Conway, K; Angold, A; Maes, H; Liu, Y; Kumar, G; Erkanli, A; Patkar, AA; Silberg, J ...
Published in: Twin Res Hum Genet
August 2015

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.

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Published In

Twin Res Hum Genet

DOI

ISSN

1832-4274

Publication Date

August 2015

Volume

18

Issue

4

Start / End Page

335 / 347

Location

England

Related Subject Headings

  • Young Adult
  • Polymorphism, Single Nucleotide
  • Mitochondrial Membrane Transport Proteins
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Genetic Predisposition to Disease
  • GTP Phosphohydrolases
 

Citation

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Adkins, D. E., Clark, S. L., Copeland, W. E., Kennedy, M., Conway, K., Angold, A., … Costello, E. J. (2015). Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood. Twin Res Hum Genet, 18(4), 335–347. https://doi.org/10.1017/thg.2015.36
Adkins, Daniel E., Shaunna L. Clark, William E. Copeland, Martin Kennedy, Kevin Conway, Adrian Angold, Hermine Maes, et al. “Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood.Twin Res Hum Genet 18, no. 4 (August 2015): 335–47. https://doi.org/10.1017/thg.2015.36.
Adkins DE, Clark SL, Copeland WE, Kennedy M, Conway K, Angold A, et al. Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood. Twin Res Hum Genet. 2015 Aug;18(4):335–47.
Adkins, Daniel E., et al. “Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood.Twin Res Hum Genet, vol. 18, no. 4, Aug. 2015, pp. 335–47. Pubmed, doi:10.1017/thg.2015.36.
Adkins DE, Clark SL, Copeland WE, Kennedy M, Conway K, Angold A, Maes H, Liu Y, Kumar G, Erkanli A, Patkar AA, Silberg J, Brown TH, Fergusson DM, Horwood LJ, Eaves L, van den Oord EJCG, Sullivan PF, Costello EJ. Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood. Twin Res Hum Genet. 2015 Aug;18(4):335–347.
Journal cover image

Published In

Twin Res Hum Genet

DOI

ISSN

1832-4274

Publication Date

August 2015

Volume

18

Issue

4

Start / End Page

335 / 347

Location

England

Related Subject Headings

  • Young Adult
  • Polymorphism, Single Nucleotide
  • Mitochondrial Membrane Transport Proteins
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Genetic Predisposition to Disease
  • GTP Phosphohydrolases