Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically influenced complex disorders that exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genomewide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (1) AD, 1224 cases and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10,000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance ( p < 5 × 10-8) for ND (rs964170 in ARHGAP10 on chromosome 4, p = 4.43 × 10-8) and three others for comorbid AD/ND (rs7530302 near MARK1on chromosome 1 ( p = 1.90 × 10-9), rs1784300 near DDX6 on chromosome 11 ( p = 2.60 × 10-9) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 × 10-8)). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top -results revealed overrepresentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be required before the detailed causes of comorbidity between AD and ND are understood.
|Number of pages||20|
|Journal||Twin Research and Human Genetics|
|State||Published - Feb 2010|