Pooled association genome scanning for alcohol dependence using 104,268 SNPs: validation and use to identify alcoholism vulnerability loci in unrelated individuals from the collaborative study on the genetics of alcoholism.

Full Abstract

Association genome scanning can identify markers for the allelic variants that contribute to vulnerability to complex disorders, including alcohol dependence. To improve the power and feasibility of this approach, we report validation of "100k" microarray-based allelic frequency assessments in pooled DNA samples. We then use this approach with unrelated alcohol-dependent versus control individuals sampled from pedigrees collected by the Collaborative Study on the Genetics of Alcoholism (COGA). Allele frequency differences between alcohol-dependent and control individuals are assessed in quadruplicate at 104,268 autosomal SNPs in pooled samples. One hundred eighty-eight SNPs provide (1) the largest allele frequency differences between dependent versus control individuals; (2) t values >or= 3 for these differences; and (3) clustering, so that 51 relatively small chromosomal regions contain at least three SNPs that satisfy criteria 1 and 2 above (Monte Carlo P = 0.00034). These positive SNP clusters nominate interesting genes whose products are implicated in cellular signaling, gene regulation, development, "cell adhesion," and Mendelian disorders. The results converge with linkage and association results for alcohol and other addictive phenotypes. The data support polygenic contributions to vulnerability to alcohol dependence. These SNPs provide new tools to aid the understanding, prevention, and treatment of alcohol abuse and dependence.(c) 2006 Wiley-Liss, Inc.

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Author information

Author/s: Johnson, Catherine (C); Drgon, Tomas (T); Liu, Qing-Rong (QR); Walther, Donna (D); Edenberg, Howard (H); Rice, John (J); Foroud, Tatiana (T); Uhl, George R (GR);

Affiliation: Molecular Neurobiology Branch, NIDA-IRP, NIH, Baltimore, Maryland 21224, USA.

Grants: U10AA008401 (Agency:NIAAA NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural

Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet), published in United States. (Language: eng)

Reference: 2006-Dec; vol 141B (issue 8) : pp 844-53

Dates: Created 2006/11/28; Completed 2007/02/13; Revised 2008/05/21;

PMID: 16894614, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Alcoholism - genetics
Chromosomes, Human - genetics
European Continental Ancestry Group - genetics
Gene Frequency
Genetic Predisposition to Disease
Genetic Screening

Genetic Screening
Genome, Human - genetics
Genomics - methods
Humans
Microarray Analysis
Polymorphism, Single Nucleotide - genetics

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