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 - PubMed (original) (raw)

Comparative Study

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

Catherine Johnson et al. Am J Med Genet B Neuropsychiatr Genet. 2006.

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.

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Figures

Figure 1

Main axes: Abuser/control ratios to the chromosomal position of each SNP for COGA alcohol dependent and control individuals. The positions of the SNPs whose data yield outlier abuser/control values are indicated by larger symbols. Supplementary axis (right of main axis): SNPs for which abuser/control differences display t values ≥ 3. Red dots designate clustered positive SNPs that display outlier abuser/control and t values. Scale: chromosomal positions based on NCBI Map Viewer coordinates and supplemental data from NETAFFYX. The vertical bar represents 25 MB.

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References

1. Bansal A. Trends in reporting of SNP associations. Lancet. 2001;358(9298):2016. - PubMed
1. Barcellos LF, Klitz W, Field LL, Tobias R, Bowcock AM, Wilson R, Nelson MP, Nagatomi J, Thomson G. Association mapping of disease loci, by use of a pooled DNA genomic screen. Am J Hum Genet. 1997;61(3):734–47. - PMC - PubMed
1. Bergen AW, Yang XR, Bai Y, Beerman MB, Goldstein AM, Goldin LR. Genomic regions linked to alcohol consumption in the Framingham Heart Study. BMC Genet. 2003;4(Suppl 1):S101. - PMC - PubMed
1. Bierut LJ, Saccone NL, Rice JP, Goate A, Foroud T, Edenberg H, Almasy L, Conneally PM, Crowe R, Hesselbrock V. Defining alcohol-related phenotypes in humans. The Collaborative Study on the Genetics of Alcoholism. Alcohol Res Health. 2002;26(3):208–13. others. - PMC - PubMed
1. Butcher LM, Meaburn E, Liu L, Fernandes C, Hill L, Al-Chalabi A, Plomin R, Schalkwyk L, Craig IW. Genotyping pooled DNA on microarrays: a systematic genome screen of thousands of SNPs in large samples to detect QTLs for complex traits. Behav Genet. 2004;34(5):549–55. - PubMed

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 - PubMed (original) (raw)