Document Detail


Autosomal linkage scan for loci predisposing to comorbid dependence on multiple substances.
MedLine Citation:
PMID:  22354695     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multiple substance dependence (MSD) trait comorbidity is common, and MSD patients are often severely affected clinically. While shared genetic risks have been documented, so far there has been no published report using the linkage scan approach to survey risk loci for MSD as a phenotype. A total of 1,758 individuals in 739 families [384 African American (AA) and 355 European American (EA) families] ascertained via affected sib-pairs with cocaine or opioid or alcohol dependence were genotyped using an array-based linkage panel of single-nucleotide polymorphism markers. Fuzzy clustering analysis was conducted on individuals with alcohol, cannabis, cocaine, opioid, and nicotine dependence for AAs and EAs separately, and linkage scans were conducted for the output membership coefficients using Merlin-regression. In EAs, we observed an autosome-wide significant linkage signal on chromosome 4 (peak lod = 3.31 at 68.3 cM; empirical autosome-wide P = 0.038), and a suggestive linkage signal on chromosome 21 (peak lod = 2.37 at 19.4 cM). In AAs, four suggestive linkage peaks were observed: two peaks on chromosome 10 (lod = 2.66 at 96.7 cM and lod = 3.02 at 147.6 cM] and the other two on chromosomes 3 (lod = 2.81 at 145.5 cM) and 9 (lod = 1.93 at 146.8 cM). Three particularly promising candidate genes, GABRA4, GABRB1, and CLOCK, are located within or very close to the autosome-wide significant linkage region for EAs on chromosome 4. This is the first linkage evidence supporting existence of genetic loci influencing risk for several comorbid disorders simultaneously in two major US populations.
Authors:
Bao-Zhu Yang; Shizhong Han; Henry R Kranzler; Lindsay A Farrer; Robert C Elston; Joel Gelernter
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-02-21
Journal Detail:
Title:  American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics     Volume:  159B     ISSN:  1552-485X     ISO Abbreviation:  Am. J. Med. Genet. B Neuropsychiatr. Genet.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-08     Completed Date:  2012-09-04     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  101235742     Medline TA:  Am J Med Genet B Neuropsychiatr Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  361-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
African Americans / genetics
Alcoholism / epidemiology,  genetics
Chromosomes, Human / genetics*
Cluster Analysis
Cocaine-Related Disorders / epidemiology,  genetics
Comorbidity
European Continental Ancestry Group / genetics
Female
Fuzzy Logic
Genetic Linkage*
Genetic Loci / genetics*
Genetic Predisposition to Disease*
Humans
Lod Score
Male
Opioid-Related Disorders / genetics
Phenotype
Substance-Related Disorders / epidemiology*,  genetics*
United States / epidemiology
Grant Support
ID/Acronym/Agency:
K01 DA024758/DA/NIDA NIH HHS; K01 DA24758/DA/NIDA NIH HHS; R01 AA011330/AA/NIAAA NIH HHS; R01 AA017535/AA/NIAAA NIH HHS; R01 AA11330/AA/NIAAA NIH HHS; R01 DA012690/DA/NIDA NIH HHS; R01 DA012849/DA/NIDA NIH HHS; R01 DA018432/DA/NIDA NIH HHS; R01 DA12690/DA/NIDA NIH HHS; R01 DA12849/DA/NIDA NIH HHS; R01 DA18432/DA/NIDA NIH HHS; U24 NS051869-02S1/NS/NINDS NIH HHS
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