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Examining sex differences in pleiotropic effects for depression and smoking using polygenic and gene‐region aggregation techniques

dc.contributor.authorSchmitz, Lauren L.
dc.contributor.authorGard, Arianna M.
dc.contributor.authorWare, Erin B.
dc.date.accessioned2019-08-09T17:15:34Z
dc.date.availableWITHHELD_14_MONTHS
dc.date.available2019-08-09T17:15:34Z
dc.date.issued2019-09
dc.identifier.citationSchmitz, Lauren L.; Gard, Arianna M.; Ware, Erin B. (2019). "Examining sex differences in pleiotropic effects for depression and smoking using polygenic and gene‐region aggregation techniques." American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 180(6): 448-468.
dc.identifier.issn1552-4841
dc.identifier.issn1552-485X
dc.identifier.urihttps://hdl.handle.net/2027.42/150605
dc.description.abstractSex differences in rates of depression are thought to contribute to sex differences in smoking initiation (SI) and number of cigarettes smoked per day (CPD). One hypothesis is that women smoke as a strategy to cope with anxiety and depression, and have difficulty quitting because of concomitant changes in hypothalamic–pituitary–adrenocortical (HPA) axis function during nicotine withdrawal states. Despite evidence of biological ties, research has not examined whether genetic factors that contribute to depression‐smoking comorbidity differ by sex. We utilized two statistical aggregation techniques—polygenic scores (PGSs) and sequence kernel association testing—to assess the degree of pleiotropy between these behaviors and moderation by sex in the Health and Retirement Study (N = 8,086). At the genome‐wide level, we observed associations between PGSs for depressive symptoms and SI, and measured SI and depressive symptoms (all p < .01). At the gene level, we found evidence of pleiotropy in FKBP5 for SI (p = .028), and sex‐specific pleiotropy in females in NR3C2 (p = .030) and CHRNA5 (p = .025) for SI and CPD, respectively. Results suggest bidirectional associations between depression and smoking may be partially accounted for by shared genetic factors, and genetic variation in genes related to HPA‐axis functioning and nicotine dependence may contribute to sex differences in SI and CPD.
dc.publisherJohn Wiley & Sons, Inc.
dc.subject.otherHPA‐axis
dc.subject.othersmoking behavior
dc.subject.othersequence kernel association testing (SKAT)
dc.subject.otherpolygenic score (PGS)
dc.subject.otherpleiotropy
dc.titleExamining sex differences in pleiotropic effects for depression and smoking using polygenic and gene‐region aggregation techniques
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelMedicine (General)
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/150605/1/ajmgb32748.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/150605/2/ajmgb32748_am.pdf
dc.identifier.doi10.1002/ajmg.b.32748
dc.identifier.sourceAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
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