Associations of prodynorphin sequence variation with alcohol dependence and related traits are phenotype-specific and sex-dependent

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Winham, Stacey J.Mayo Clin, Hlth Sci Res, Rochester, MN USA. (author)

Associations of prodynorphin sequence variation with alcohol dependence and related traits are phenotype-specific and sex-dependent

Article/chapterEnglish2015

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2015-10-27
Springer Science and Business Media LLC,2015
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LIBRIS-ID:oai:DiVA.org:uu-267194
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-267194URI
https://doi.org/10.1038/srep15670DOI

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Language:English
Summary in:English

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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.

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MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine hsv//eng

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Preuss, Ulrich W.Univ Halle Wittenberg, Dept Psychiat Psychotherapy & Psychosomat, D-06108 Halle, Germany. (author)
Geske, Jennifer R.Mayo Clin, Hlth Sci Res, Rochester, MN USA. (author)
Zill, PeterLudwig Maximilians Univ Munchen, Dept Psychiat, Sect Psychiat Genet & Neurochem, Munich, Germany. (author)
Heit, John A.Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. (author)
Bakalkin, GeorgyUppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)gueba200 (author)
Biernacka, Joanna M.Mayo Clin, Hlth Sci Res, Rochester, MN USA.;Mayo Clin, Psychiat & Psychol, Rochester, MN 55902 USA. (author)
Karpyak, Victor M.Mayo Clin, Psychiat & Psychol, Rochester, MN 55902 USA. (author)
Mayo Clin, Hlth Sci Res, Rochester, MN USA.Univ Halle Wittenberg, Dept Psychiat Psychotherapy & Psychosomat, D-06108 Halle, Germany. (creator_code:org_t)

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