Genomewide suggestive linkage of opioid dependence to chromosome 14q.
paper
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- Authors
- Lachman, Herbert M; Fann, Cathy S J; Bartzis, Michael; Evgrafov, Oleg V; Rosenthal, Richard N; Nunes, Edward V; Miner, Christian; Santana, Maria; Gaffney, Jebediah; Riddick, Amy; Hsu, Chia-Lin; Knowles, James A
- Year
- 2007
- Journal
- Human molecular genetics
- PMID
- 17409192
- DOI
- 10.1093/hmg/ddm081
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 (NPL(Caucasian) = 0.05 and NPL(African 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 (NPL(female) = 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.
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