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dc.contributor.advisorBlacker, Deborahen_US
dc.contributor.authorLin, Yen-Fengen_US
dc.date.accessioned2018-03-23T19:09:40Z
dash.embargo.terms2019-03-01en_US
dc.date.created2018-03en_US
dc.date.issued2018-01-19en_US
dc.date.submitted2018en_US
dc.identifier.citationLin, Yen-Feng. 2018. Genetic Overlap and Causal Mediation Relationship Between Psychiatric and Non-Psychiatric Phenotypes. Doctoral dissertation, Harvard T.H. Chan School of Public Health.en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:35083763
dc.description.abstractGenome-wide genotyping studies are providing evidence that psychiatric disorders are truly polygenic, that is they have a genetic architecture of many genetic variants. Cross-trait polygenic analysis has been applied to identifying genetic correlations between psychiatric and non-psychiatric phenotypes. However, causal models between shared genetic factors and the genetically-correlated phenotypes are mostly unclear. We used cross-trait polygenic risk score (PRS) association analysis to examine the genetic overlap between two phenotypes. We then performed causal mediation analysis to identify the causal relationship between common genetic variants and two genetically correlated traits. We examined if the effect of polygenic risk on one trait (i.e., the outcome) was mediated by the other trait (i.e., the mediator). In Chapter 1, we examined the relationship between PRS for psychotic illness or cognitive ability, event-related potential (ERP), and severity of psychotic symptoms. A phenotype of global impairment on multiple ERP measures is associated with positive symptoms of psychosis as well as polygenic influences on educational attainment and, to a lesser extent, schizophrenia. We also observed a positive association between education PRS and positive symptoms that was almost entirely mediated by effects on the globally impaired ERP phenotype. In Chapter 2, we examined the relationship between PRS for Alzheimer’s dementia, vascular pathologies, and late-life cognitive function. Our findings support the hypothesis of a genetic overlap, mostly due to APOE, between vascular pathologies and AD dementia. The polygenic genetic effect on late-life cognition is partially but significantly mediated by cerebral microbleeds, white matter lesion load, and coronary artery calcification. In Chapter 3, we examined the relationship between PRS for coronary heart disease, psychological attitudes, and liability to coronary heart disease. Our findings suggest a genetic overlap between optimism and CHD in older women of European ancestry. The polygenic genetic effect on CHD is modestly though significantly mediated by optimism.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoenen_US
dash.licenseLAAen_US
dc.subjectHealth Sciences, Epidemiologyen_US
dc.subjectHealth Sciences, Mental Healthen_US
dc.titleGenetic Overlap and Causal Mediation Relationship Between Psychiatric and Non-Psychiatric Phenotypesen_US
dc.typeThesis or Dissertationen_US
dash.depositing.authorLin, Yen-Fengen_US
dash.embargo.until2019-03-01
thesis.degree.date2018en_US
thesis.degree.grantorHarvard T.H. Chan School of Public Healthen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Science (SD)en_US
dc.contributor.committeeMemberSmoller, Jordan W.en_US
dc.contributor.committeeMemberBetensky, Rebeccaen_US
dc.contributor.committeeMemberPrice, Alkesen_US
dc.type.materialtexten_US
thesis.degree.departmentEpidemiologyen_US
dash.identifier.vireohttp://etds.lib.harvard.edu/hsph/admin/view/217en_US
dc.description.keywordspolygenic risk score, GWAS, mediation, causal mechanismen_US
dash.author.emaillinyenfeng@gmail.comen_US
dash.identifier.orcid0000-0003-3017-6026en_US
dash.contributor.affiliatedLin, Yen-Feng
dc.identifier.orcid0000-0003-3017-6026


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