| Autosomal linkage scan for loci predisposing to comorbid dependence on multiple substances. | |
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MedLine Citation:
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PMID: 22354695 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Bao-Zhu Yang; Shizhong Han; Henry R Kranzler; Lindsay A Farrer; Robert C Elston; Joel Gelernter |
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Publication Detail:
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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:
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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:
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Created Date: 2012-05-08 Completed Date: 2012-09-04 Revised Date: 2013-05-13 |
Medline Journal Info:
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Nlm Unique ID: 101235742 Medline TA: Am J Med Genet B Neuropsychiatr Genet Country: United States |
Other Details:
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Languages: eng Pagination: 361-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Wiley Periodicals, Inc. |
Affiliation:
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Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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African Americans
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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:
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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 DA12690/DA/NIDA NIH HHS; R01 DA12849/DA/NIDA NIH HHS; R01 DA18432/DA/NIDA NIH HHS; U24 NS051869-02S1/NS/NINDS NIH HHS |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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