Human Molecular Genetics Advance Access originally published online on April 4, 2007
Human Molecular Genetics 2007 16(11):1327-1334; doi:10.1093/hmg/ddm081
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Genomewide suggestive linkage of opioid dependence to chromosome 14q
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1 Division of Basic Research, Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine Bronx, NY 10461, USA, 2 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China, 3 Department of Psychiatry, New York State Psychiatric Institute, 4 Division on Substance Abuse, Department of Psychiatry, New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA, 5 Department of Psychiatry, St Luke's Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY 10019, USA and 6 Department of Psychiatry, Beth Israel Medical Center, New York, NY 10003-3896, USA
* To whom correspondence should be addressed at: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Tel: +1 7184302428; Fax: +1 7184308772; Email: lachman{at}aecom.yu.edu
Received November 1, 2006; Accepted March 26, 2007
The genetic predisposition to addiction to opioids and other substances is transmitted as a complex genetic trait, which investigators are attempting to characterize using genetic linkage and association. We now report a high-density genome-wide linkage study of opioid dependence. We ascertained 305 DSM-IV opioid dependent affected sibling pairs from an ethnically mixed population of methadone maintained subjects and genotyped their DNA using Affymetrix 10K v2 arrays. Analysis with MERLIN identified a region on chromosome 14q with a non-parametric lod (NPL) of 3.30. Secondary analyses indicated that this locus was relatively specific to the self-identified Puerto Rican subset, as the NPL increased from 3.30 to 5.00 (NPLCaucasian = 0.05 and NPLAfrican Amer. = 0.15). The 14q peak encompasses the NRXN3 gene (neurexin 3), which was previously identified as a potential candidate gene for addiction. Secondary analyses also identified several regions with gender-specific NPL scores greater than 2.00. The most significant was a peak on (10q) that increased from 0.90 to 3.22 when only males were considered (NPLfemale = 0.05). Our linkage data suggest specific chromosomal loci for future fine-mapping genetic analysis and support the hypothesis that ethnic and gender specific genes underlie addiction susceptibility.
These authors contributed equally to this study.
Present address: Zilkha Neurogenetic Institute, Department of Psychiatry, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
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