A genomewide association study of nicotine and alcohol dependence in Australian and Dutch populations

Lind, Penelope A., Macgregor, Stuart, Vink, Jacqueline M., Pergadia, Michele L., Hansell, Narelle K., de Moor, Marleen H. M., Smit, August B., Hottenga, Jouke-Jan, Richter, Melinda M., Heath, Andrew C., Martin, Nicholas G., Willemsen, Gonneke, de Geus, Eco J. C., Vogelzangs,Nicole, Penninx, Brenda W., Whitfield, John B., Montgomery, Grant W., Boomsma, Dorret I. and Madden, Pamela A. F. (2010) A genomewide association study of nicotine and alcohol dependence in Australian and Dutch populations. Twin Research And Human Genetics, 13 1: 10-29. doi:10.1375/twin.13.1.10

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Author Lind, Penelope A.
Macgregor, Stuart
Vink, Jacqueline M.
Pergadia, Michele L.
Hansell, Narelle K.
de Moor, Marleen H. M.
Smit, August B.
Hottenga, Jouke-Jan
Richter, Melinda M.
Heath, Andrew C.
Martin, Nicholas G.
Willemsen, Gonneke
de Geus, Eco J. C.
Penninx, Brenda W.
Whitfield, John B.
Montgomery, Grant W.
Boomsma, Dorret I.
Madden, Pamela A. F.
Title A genomewide association study of nicotine and alcohol dependence in Australian and Dutch populations
Journal name Twin Research And Human Genetics   Check publisher's open access policy
ISSN 1832-4274
Publication date 2010-02
Sub-type Article (original research)
DOI 10.1375/twin.13.1.10
Volume 13
Issue 1
Start page 10
End page 29
Total pages 20
Place of publication Bowen Hills, QLD, Australia
Publisher Australian Academic Press
Collection year 2011
Language eng
Formatted 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 × 10−8) for ND (rs964170 in ARHGAP10 on chromosome 4, p = 4.43 × 10−8) and three others for comorbid AD/ND (rs7530302 near MARK1 on 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.
Copyright © Australian Academic Press 2011 All Rights Reserved.
Keyword Addiction
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 58 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 30 Mar 2011, 12:56:18 EST by Debbie Banks on behalf of School of Medicine