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

Winham, Stacey J. (författare)
Mayo Clin, Hlth Sci Res, Rochester, MN USA.
Preuss, Ulrich W. (författare)
Univ Halle Wittenberg, Dept Psychiat Psychotherapy & Psychosomat, D-06108 Halle, Germany.
Geske, Jennifer R. (författare)
Mayo Clin, Hlth Sci Res, Rochester, MN USA.
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Zill, Peter (författare)
Ludwig Maximilians Univ Munchen, Dept Psychiat, Sect Psychiat Genet & Neurochem, Munich, Germany.
Heit, John A. (författare)
Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
Bakalkin, Georgy (författare)
Uppsala universitet,Institutionen för farmaceutisk biovetenskap
Biernacka, Joanna M. (författare)
Mayo Clin, Hlth Sci Res, Rochester, MN USA.;Mayo Clin, Psychiat & Psychol, Rochester, MN 55902 USA.
Karpyak, Victor M. (författare)
Mayo Clin, Psychiat & Psychol, Rochester, MN 55902 USA.
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Mayo Clin, Hlth Sci Res, Rochester, MN USA Univ Halle Wittenberg, Dept Psychiat Psychotherapy & Psychosomat, D-06108 Halle, Germany. (creator_code:org_t)
2015
2015
Engelska.
Ingår i: ; 5
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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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.

Ämnesord

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

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