Referenced in: none

Automatically associated channels: Kir2.3

Title: A genomewide association study of nicotine and alcohol dependence in Australian and dutch populations.

Authors: Penelope A Lind, Stuart Macgregor, Jacqueline M Vink, Michele L Pergadia, Narelle K Hansell, Marleen H M de Moor, August B Smit, Jouke-Jan Hottenga, Melinda M Richter, Andrew C Heath, Nicholas G Martin, Gonneke Willemsen, Eco J C de Geus, Nicole Vogelzangs, Brenda W Penninx, John B Whitfield, Grant W Montgomery, Dorret I Boomsma, Pamela A F Madden

Journal, date & volume: Twin Res Hum Genet, 2010 Feb , 13, 10-29

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20158304

Abstract
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 x 10(-8)) for ND (rs964170 in ARHGAP10 on chromosome 4, p = 4.43 x 10(-8)) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p = 1.90 x 10(-9)), rs1784300 near DDX6 on chromosome 11 (p = 2.60 x 10(-9)) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 x 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.