Genomewide suggestive linkage of opioid dependence to chromosome 14q.
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.
Lachman
Herbert M
HM
Division of Basic Research, Department of Psychiatry and Behavioral Sciences, Albert Einstein College of MedicineBronx, NY 10461, USA. lachman@aecom.yu.edu
Fann
Cathy S J
CS
Bartzis
Michael
M
Evgrafov
Oleg V
OV
Rosenthal
Richard N
RN
Nunes
Edward V
EV
Miner
Christian
C
Santana
Maria
M
Gaffney
Jebediah
J
Riddick
Amy
A
Hsu
Chia-Lin
CL
Knowles
James A
JA
D000701:Analgesics, Opioid; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D035781:Siblings; D019966:Substance-Related Disorders / Q000235:genetics*
D000701:Analgesics, Opioid