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A Genomewide Association Study of Nicotine and Alcohol Dependence in Australian and Dutch Populations

Published online by Cambridge University Press:  21 January 2016

Penelope A. Lind
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia
Stuart Macgregor
Affiliation:
Queensland Statistical Genetics, Queensland Institute of Medical Research, Brisbane, Australia
Jacqueline M. Vink
Affiliation:
Department of Biological Psychology, VU University, Amsterdam, Netherlands
Michele L Pergadia
Affiliation:
Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
Narelle K. Hansell
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia
Marleen H. M. de Moor
Affiliation:
Department of Biological Psychology, VU University, Amsterdam, Netherlands
August B. Smit
Affiliation:
Department of Molecular and Cellular Neurobiology, VU University, Amsterdam, Netherlands
Jouke-Jan Hottenga
Affiliation:
Department of Biological Psychology, VU University, Amsterdam, Netherlands
Melinda M. Richter
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia
Andrew C. Heath
Affiliation:
Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
Nicholas G. Martin
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia
Gonneke Willemsen
Affiliation:
Department of Biological Psychology, VU University, Amsterdam, Netherlands
Eco J. C. de Geus
Affiliation:
Department of Biological Psychology, VU University, Amsterdam, Netherlands
Nicole Vogelzangs
Affiliation:
Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, Netherlands
Brenda W. Penninx
Affiliation:
Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, Netherlands
John B. Whitfield
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia
Grant W. Montgomery
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia
Dorret I. Boomsma
Affiliation:
Department of Biological Psychology, VU University, Amsterdam, Netherlands
Pamela A. F. Madden
Affiliation:
Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA

Extract

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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.

Type
Articles
Copyright
Copyright © Cambridge University Press 2010

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