<h3>Context</h3> Alcohol dependence is a serious and common public health problem. It is well established that genetic factors play a major role in the development of this disorder. Identification of genes that contribute to alcohol dependence will improve our understanding of the mechanisms that underlie this disorder. <h3>Objective</h3> To identify susceptibility genes for alcohol dependence through a genome-wide association study (GWAS) and a follow-up study in a population of German male inpatients with an early age at onset. <h3>Design</h3> The GWAS tested 524 396 single-nucleotide polymorphisms (SNPs). All SNPs with<i>P</i> &lt; 10<sup>−4</sup>were subjected to the follow-up study. In addition, nominally significant SNPs from genes that had also shown expression changes in rat brains after long-term alcohol consumption were selected for the follow-up step. <h3>Setting</h3> Five university hospitals in southern and central Germany. <h3>Participants</h3> The GWAS included 487 male inpatients with alcohol dependence as defined by the<i>DSM-IV</i>and an age at onset younger than 28 years and 1358 population-based control individuals. The follow-up study included 1024 male inpatients and 996 age-matched male controls. All the participants were of German descent. <h3>Main Outcome Measures</h3> Significant association findings in the GWAS and follow-up study with the same alleles. <h3>Results</h3> The GWAS produced 121 SNPs with nominal<i>P</i> &lt; 10<sup>−4</sup>. These, together with 19 additional SNPs from homologues 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, 2 closely linked intergenic SNPs met genome-wide significance (rs7590720,<i>P</i> = 9.72 × 10<sup>−9</sup>; rs1344694,<i>P</i> = 1.69 × 10<sup>−8</sup>). They are located on chromosome region 2q35, which has been implicated in linkage studies for alcohol phenotypes. Nine SNPs were located in genes, including the<i>CDH13</i>and<i>ADH1C</i>genes, that have been reported to be associated with alcohol dependence. <h3>Conclusions</h3> 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.

Genome-wide Association Study of Alcohol Dependence