Associations of prodynorphin sequence variation with alcohol dependence and related traits are phenotype-specific and sex-dependent
2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 15670Article in journal (Refereed) Published
We previously demonstrated that prodynorphin (PDYN) haplotypes and single nucleotide polymorphism (SNP) rs2281285 are associated with alcohol dependence and the propensity to drink in negative emotional states, and recent studies suggest that PDYN gene effects on substance dependence risk may be sex-related. We examined sex-dependent associations of PDYN variation with alcohol dependence and related phenotypes, including negative craving, time until relapse after treatment and the length of sobriety episodes before seeking treatment, in discovery and validation cohorts of European ancestry. We found a significant haplotype-by-sex interaction (p = 0.03), suggesting association with alcohol dependence in males (p = 1E-4) but not females. The rs2281285G allele increased risk for alcohol dependence in males in the discovery cohort (OR = 1.49, p = 0.002), with a similar trend in the validation cohort (OR = 1.35, p = 0.086). However, rs2281285 showed a trend towards association with increased negative craving in females in both the discovery (beta = 10.16, p = 0.045) and validation samples (OR = 7.11, p = 0.066). In the discovery cohort, rs2281285 was associated with time until relapse after treatment in females (HR = 1.72, p = 0.037); in the validation cohort, it was associated with increased length of sobriety episodes before treatment in males (beta = 13.49, p = 0.001). Our findings suggest that sex-dependent effects of PDYN variants in alcohol dependence are phenotype-specific.
Place, publisher, year, edition, pages
2015. Vol. 5, 15670
IdentifiersURN: urn:nbn:se:uu:diva-267194DOI: 10.1038/srep15670ISI: 000363447000001PubMedID: 26502829OAI: oai:DiVA.org:uu-267194DiVA: diva2:872560
FunderNIH (National Institute of Health), P20 AA17830ZNIH (National Institute of Health), K12 HD65987Swedish Research CouncilSwedish Research Council FormasNIH (National Institute of Health), HG04735