Skip Navigation


Human Molecular Genetics Advance Access originally published online on November 3, 2006
Human Molecular Genetics 2006 15(24):3498-3507; doi:10.1093/hmg/ddl426
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
15/24/3498    most recent
ddl426v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Google Scholar
Right arrow Articles by Gelernter, J.
Right arrow Articles by Farrer, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gelernter, J.
Right arrow Articles by Farrer, L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Haplotype spanning TTC12 and ANKK1, flanked by the DRD2 and NCAM1 loci, is strongly associated to nicotine dependence in two distinct American populations

Joel Gelernter1,2,3,4,*, Yi Yu5, Roger Weiss10,11, Kathleen Brady12, Carolien Panhuysen5,6, Bao-zhu Yang1,4, Henry R. Kranzler13 and Lindsay Farrer5,6,7,8,9

1 Division of Human Genetics, Department of Psychiatry, 2 Department of Neurobiology, 3 Department of Genetics and 4 VA CT Healthcare Center, Yale University School of Medicine, VA CT 116A2, 950 Campbell Avenue, West Haven, CT 06516, USA, 5 Department of Medicine (Genetics Program), 6 Department of Biostatistics, 7 Department of Neurology, 8 Department of Genetics & Genomics, and 9 Department of Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA, 10 Alcohol and Drug Abuse Treatment Program, McLean Hospital, Belmont, MA, USA, 11 Department of Psychiatry, Harvard Medical School, Boston, MA, USA, 12 Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA and 13 Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA

* To whom correspondence should be addressed. Tel: +1 2039325711, ext 3590; Fax: , +1 2039374741; Email: joel.gelernter{at}yale.edu

Received August 24, 2006; Accepted October 26, 2006

Nicotine dependence (ND) is a moderately heritable trait. We ascertained a set of 1615 subjects in 632 families [319 African-American (AA) and 313 European-American (EA)] based on affected sibling pairs with cocaine or opioid dependence. Subjects were interviewed with the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). Previously, we identified a modest linkage peak (LOD score =1.97) for ND in the EA part of the sample on chromosome 11q23, a region that includes the NCAM1–TTC12–ANKK1–DRD2 gene cluster. DRD2 and NCAM1 are functional candidate genes for substance dependence; the TTC12 and ANKK1 loci are not well characterized. We genotyped a set of 43 single nucleotide polymorphisms (SNPs) spanning this region, and performed family-based association and haplotype analysis. There was relatively weak evidence for association of the flanking DRD2 and NCAM1 markers to ND, but very strong evidence of association of multiple SNPs at TTC12 and ANKK1 in both populations (minimal P=0.0007 in AAs and minimal P=0.00009 in EAs), and in the pooled sample, as well as strong evidence for highly significant association of a single haplotype spanning TTC12 and ANKK1 to ND in the pooled sample (P=0.0000001). We conclude that a risk locus for ND, important both in AAs and EAs, maps to a region that spans TTC12 and ANKK1. Functional studies of these loci are warranted. These results provide additional information useful in evaluating the many earlier discrepant findings regarding association of DRD2 with substance dependence.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
B.-Z. Yang, H. R. Kranzler, H. Zhao, J. R. Gruen, X. Luo, and J. Gelernter
Association of haplotypic variants in DRD2, ANKK1, TTC12 and NCAM1 to alcohol dependence in independent case control and family samples
Hum. Mol. Genet., December 1, 2007; 16(23): 2844 - 2853.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.