title: Sex-specific linkage scans in opioid dependence.
abstract: Sex influences risk for opioid dependence (OD). We hypothesized that sex might interact with genetic loci that influence the risk for OD. Therefore we performed an analysis to identify sex-specific genomic susceptibility regions for OD using linkage. Over 6,000 single nucleotide polymorphism (SNP) markers were genotyped for 1,758 African- and European-American (AA and EA) individuals from 739 families, ascertained via affected sib-pairs with OD and/or cocaine dependence. Autosomewide non-parametric linkage scans, stratified by sex and population, were performed. We identified one significant linkage region, segregating with OD in EA men, at 71.1 cM on chromosome 4 (LOD = 3.29; point-wise P = 0.00005; empirical autosome-wide P = 0.042), which significantly differed from the linkage signal at the same location in EA women (empirical P = 0.002). Three suggestive linkage signals were identified at 181.3 cM on chromosome 7 (LOD = 2.18), 104 cM on chromosome 11 (LOD = 1.85), and 60.9 cM on chromosome 16 (LOD = 1.93) in EA women. In AA men, four suggestive linkage signals were detected at 201.1 cM on chromosome 3 (LOD = 2.32), 152.9 cM on chromosome 6 (LOD = 1.86), 16.8 cM on chromosome 7 (LOD = 1.95), and 36.1 cM on chromosome 17 (LOD = 1.99). The significant region, mapping to 4q12-4q13.1, harbors several OD candidate genes with interconnected functionality, including VEGFR, CLOCK, PDCL2, NMU, NRSF, and IGFBP7. In conclusion, these results provide an evidence for the existence of sex-specific and population-specific differences in OD. Furthermore, these results provide positional information that will facilitate the use of targeted next-generation sequencing to search for genes that contribute to sex-specific differences in OD. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.|VA CT Healthcare Center, West Haven, Connecticut.
authors.forename: Bao-Zhu
authors.initials: BZ
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, Iowa.
authors.forename: Shizhong
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine and VISN 4 MIRECC, Crescenz VAMC, Philadelphia, Pennsylvania.
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, California.
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Palmer
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.|VA CT Healthcare Center, West Haven, Connecticut.|Departments of Genetics and Neuroscience, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D044383:Black People / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods; D019970:Cocaine-Related Disorders / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D044465:White People / Q000235:genetics
keywords: 4q12; 4q13.1; linkage analysis; opioid dependence; sex-specific