H2 haplotype at chromosome 17q21.31 protects against childhood sexual abuse-associated risk for alcohol consumption and dependence

Nelson, Elliot C., Agrawal, Arpana, Pergadia, Michele L., Wang, Jen C., Whitfield, John B., Saccone, F. Scott, Kern, Jason, Grant, Julia D., Schrage, Andrew J., Rice, John P., Montgomery, Grant W., Heath, Andrew C, Goate, Alison M., Martin, Nicholas G. and Madden, Pamela A. F. (2010) H2 haplotype at chromosome 17q21.31 protects against childhood sexual abuse-associated risk for alcohol consumption and dependence. Addiction Biology, 15 1: 1-11. doi:10.1111/j.1369-1600.2009.00181.x


Author Nelson, Elliot C.
Agrawal, Arpana
Pergadia, Michele L.
Wang, Jen C.
Whitfield, John B.
Saccone, F. Scott
Kern, Jason
Grant, Julia D.
Schrage, Andrew J.
Rice, John P.
Montgomery, Grant W.
Heath, Andrew C
Goate, Alison M.
Martin, Nicholas G.
Madden, Pamela A. F.
Title H2 haplotype at chromosome 17q21.31 protects against childhood sexual abuse-associated risk for alcohol consumption and dependence
Journal name Addiction Biology   Check publisher's open access policy
ISSN 1355-6215
1369-1600
Publication date 2010-01
Year available 2009
Sub-type Article (original research)
DOI 10.1111/j.1369-1600.2009.00181.x
Volume 15
Issue 1
Start page 1
End page 11
Total pages 11
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Animal research supports a central role for corticotropin-releasing factor (CRF) in actions of ethanol on brain function. An examination of alcohol consumption in adolescents reported a significant genotype × environment (G × E) interaction involving rs1876831, a corticotropin-releasing hormone receptor 1 (CRHR1) polymorphism, and negative events. CRHR1 and at least four other genes are located at 17q21.31 in an extremely large block of high linkage disequilibrium resulting from a local chromosomal inversion; the minor allele of rs1876831 is contained within the H2 haplotype. Here, we examine whether G × E interactions involving this haplotype and childhood sexual abuse (CSA) are associated with risk for alcohol consumption and dependence in Australian participants (n = 1128 respondents from 476 families) of the Nicotine Addiction Genetics project. Telephone interviews provided data on DSM-IV alcohol dependence diagnosis and CSA and enabled calculation of lifetime alcohol consumption factor score (ACFS) from four indices of alcohol consumption. Individuals reporting a history of CSA had significantly higher ACFS and increased risk for alcohol dependence. A significant G × E interaction was found for ACFS involving the H2 haplotype and CSA (P < 0.017). A similar G × E interaction was associated with protective effects against alcohol dependence risk (odds ratio 0.42; 95% confidence interval 0.20–0.89). For each outcome, no significant CSA-associated risk was observed in H2 haplotype carriers. These findings support conducting further investigation of the H2 haplotype to determine the gene(s) responsible. Our results also suggest that severe early trauma may prove to be an important clinical covariate in the treatment of alcohol dependence.
Keyword Alcohol dependence
Association
Childhood sexual abuse
CRHR1
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Article first published online: 29 OCT 2009

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 39 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 43 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 09 Nov 2011, 15:00:55 EST by Miss Kristy Reid on behalf of School of Medicine