A Genomewide Association Study of Nicotine and Alcohol Dependence in Australian and Dutch Populations
pmid: 20158304
pmc: PMC3070599
A Genomewide Association Study of Nicotine and Alcohol Dependence in Australian and Dutch Populations
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 ARHGAPlOon 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 overrepre-sentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be requirec before the detailed causes of comorbidity between AC and ND are understood.
- Erasmus University Rotterdam Netherlands
- University of Queensland Australia
- Amsterdam UMC Netherlands
- University of Mary United States
- QIMR Berghofer Medical Research Institute Australia
Netherlands Twin Register (NTR), Adult, Male, 2716 Genetics (clinical), Addiction, Comorbidity, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, 2729 Obstetrics and Gynaecology, DEAD-box RNA Helicases, SDG 3 - Good Health and Well-being, Proto-Oncogene Proteins, Genetics, Diseases in Twins, Humans, Genetic Predisposition to Disease, Registries, Aged, Netherlands, Smoking, GTPase-Activating Proteins, Australia, 820, Tobacco Use Disorder, Middle Aged, Perinatology, and Child Health, Alcoholism, Case-Control Studies, Female, 2735 Pediatrics, Alcohol, Genome-Wide Association Study
Netherlands Twin Register (NTR), Adult, Male, 2716 Genetics (clinical), Addiction, Comorbidity, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, 2729 Obstetrics and Gynaecology, DEAD-box RNA Helicases, SDG 3 - Good Health and Well-being, Proto-Oncogene Proteins, Genetics, Diseases in Twins, Humans, Genetic Predisposition to Disease, Registries, Aged, Netherlands, Smoking, GTPase-Activating Proteins, Australia, 820, Tobacco Use Disorder, Middle Aged, Perinatology, and Child Health, Alcoholism, Case-Control Studies, Female, 2735 Pediatrics, Alcohol, Genome-Wide Association Study
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