Genomewide suggestive linkage of opioid dependence to chromosome 14q

Herbert M. Lachman, Cathy S.J. Fann, Michael Bartzis, Oleg V. Evgrafov, Richard N. Rosenthal, Edward V. Nunes, Christian Miner, Maria Santana, Jebediah Gaffney, Amy Riddick, Chia Lin Hsu, James A. Knowles

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

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 = 5 0.05 and NPLAfrican Amer. = 5 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 = 5 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.

Original languageEnglish (US)
Pages (from-to)1327-1334
Number of pages8
JournalHuman molecular genetics
Volume16
Issue number11
DOIs
StatePublished - Jun 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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