Exploring intra-diagnosis heterogeneity and inter-diagnosis commonality in genetic architectures of bipolar disorders: association of polygenic risks of major psychiatric illnesses and lifetime phenotype dimensions.
Ji Hyun Baek, Dongbin Lee, Dongeun Lee, Hyewon Jeong, Eun-Young Cho, Tae Hyon Ha, Kyooseob Ha, Kyung Sue Hong
{"title":"Exploring intra-diagnosis heterogeneity and inter-diagnosis commonality in genetic architectures of bipolar disorders: association of polygenic risks of major psychiatric illnesses and lifetime phenotype dimensions.","authors":"Ji Hyun Baek, Dongbin Lee, Dongeun Lee, Hyewon Jeong, Eun-Young Cho, Tae Hyon Ha, Kyooseob Ha, Kyung Sue Hong","doi":"10.1017/S003329172400120X","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Bipolar disorder (BD) shows heterogeneous illness presentation both cross-sectionally and longitudinally. This phenotypic heterogeneity might reflect underlying genetic heterogeneity. At the same time, overlapping characteristics between BD and other psychiatric illnesses are observed at clinical and biomarker levels, which implies a shared biological mechanism between them. Incorporating these two issues in a single study design, this study investigated whether phenotypically heterogeneous subtypes of BD have a distinct polygenic basis shared with other psychiatric illnesses.</p><p><strong>Methods: </strong>Six lifetime phenotype dimensions of BD identified in our previous study were used as target phenotypes. Associations between these phenotype dimensions and polygenic risk scores (PRSs) of major psychiatric illnesses from East Asian (EA) and other available populations were analyzed.</p><p><strong>Results: </strong>Each phenotype dimension showed a different association pattern with PRSs of mental illnesses. PRS for EA schizophrenia showed a significant negative association with the cyclicity dimension (<i>p</i> = 0.044) but a significant positive association with the psychotic/irritable mania dimension (<i>p</i> = 0.001). PRS of EA major depressive disorder demonstrated a significant negative association with the elation dimension (<i>p</i> = 0.003) but a significant positive association with the comorbidity dimension (<i>p</i> = 0.028).</p><p><strong>Conclusion: </strong>This study demonstrates that well-defined phenotype dimensions of lifetime-basis in BD have distinct genetic risks shared with other major mental illnesses. This finding supports genetic heterogeneity in BD and suggests a pleiotropy among BD subtypes and other psychiatric disorders beyond BD. Further genomic analyses adopting deep phenotyping across mental illnesses in ancestrally diverse populations are warranted to clarify intra-diagnosis heterogeneity and inter-diagnoses commonality issues in psychiatry.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":null,"pages":null},"PeriodicalIF":5.9000,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychological Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1017/S003329172400120X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Bipolar disorder (BD) shows heterogeneous illness presentation both cross-sectionally and longitudinally. This phenotypic heterogeneity might reflect underlying genetic heterogeneity. At the same time, overlapping characteristics between BD and other psychiatric illnesses are observed at clinical and biomarker levels, which implies a shared biological mechanism between them. Incorporating these two issues in a single study design, this study investigated whether phenotypically heterogeneous subtypes of BD have a distinct polygenic basis shared with other psychiatric illnesses.
Methods: Six lifetime phenotype dimensions of BD identified in our previous study were used as target phenotypes. Associations between these phenotype dimensions and polygenic risk scores (PRSs) of major psychiatric illnesses from East Asian (EA) and other available populations were analyzed.
Results: Each phenotype dimension showed a different association pattern with PRSs of mental illnesses. PRS for EA schizophrenia showed a significant negative association with the cyclicity dimension (p = 0.044) but a significant positive association with the psychotic/irritable mania dimension (p = 0.001). PRS of EA major depressive disorder demonstrated a significant negative association with the elation dimension (p = 0.003) but a significant positive association with the comorbidity dimension (p = 0.028).
Conclusion: This study demonstrates that well-defined phenotype dimensions of lifetime-basis in BD have distinct genetic risks shared with other major mental illnesses. This finding supports genetic heterogeneity in BD and suggests a pleiotropy among BD subtypes and other psychiatric disorders beyond BD. Further genomic analyses adopting deep phenotyping across mental illnesses in ancestrally diverse populations are warranted to clarify intra-diagnosis heterogeneity and inter-diagnoses commonality issues in psychiatry.
期刊介绍:
Now in its fifth decade of publication, Psychological Medicine is a leading international journal in the fields of psychiatry, related aspects of psychology and basic sciences. From 2014, there are 16 issues a year, each featuring original articles reporting key research being undertaken worldwide, together with shorter editorials by distinguished scholars and an important book review section. The journal''s success is clearly demonstrated by a consistently high impact factor.