Genome-wide association study of alcohol dependence

By J. Treutlein, S. Cichon, M. Ridinger, N. Wodarz, M. Soyka, P. Zill, Wolfgang Maier, R. Moessner, W. Gaebel, N. Dahmen and 19 more. Archives of General Psychiatry, 2009

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Context Identification of genes contributing to alcohol dependence will improve our understanding of the mechanisms underlying this disorder. Objective To identify susceptibility genes for alcohol dependence through a genome-wide association study (GWAS) and follow-up study in a population of German male inpatients with an early age at onset. Design The GWAS included 487 male inpatients with DSM-IV alcohol dependence with an age at onset below 28 years and 1,358 population based control individuals. The follow-up study included 1,024 male inpatients and 996 age-matched male controls. All subjects were of German descent. The GWAS tested 524,396 single nucleotide polymorphisms (SNPs). All SNPs with p<10-4 were subjected to the follow-up study. In addition, nominally significant SNPs from those genes that had also shown expression changes in rat brains after chronic alcohol consumption were selected for the follow-up step. Results The GWAS produced 121 SNPs with nominal p<10-4. These, together with 19 additional SNPs from homologs of rat genes showing differential expression, were genotyped in the follow-up sample. Fifteen SNPs showed significant association with the same allele as in the GWAS. In the combined analysis, two closely linked intergenic SNPs met genome-wide significance (rs7590720 p=9.72×10-9; rs1344694 p=1.69×10-8). They are located on chromosome 2q35, a region which has been implicated in linkage studies for alcohol phenotypes. Nine SNPs were located in genes, including CDH13 and ADH1C genes which have been reported to be associated with alcohol dependence. Conclusion This is the first GWAS and follow-up study to identify a genome-wide significant association in alcohol dependence. Further independent studies are required to confirm these findings.

Subfields: Epidemiology, Genetics, Pathology and Forensic Medicine

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Citations in the corpus

Understanding the contribution of synonymous mutations to human disease (2011, background): “Finally, GWASs are finding that, besides the synonymous mutations in the coding regions of genes, mutations in non-coding and intergenic regions are associated with disease”
A genome-wide scan for common alleles affecting risk for autism (2010, methodology): “A control group, namely subjects from the Study on Addiction: Genetics and Environment (SAGE), was chosen because it was genotyped with Illumina Human 1M-single Infinium BeadChip (23).”