Baek Ji Hyun, Lee Dongbin, Lee Dongeun, Jeong Hyewon, Cho Eun-Young, Ha Tae Hyon, Ha Kyooseob, Hong Kyung Sue
Department of Psychiatry, Sunkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
Dauten Family Center for Bipolar Treatment Innovation, Massachusetts General Hospital, Boston, USA.
Psychol Med. 2024 Aug;54(11):3082-3088. doi: 10.1017/S003329172400120X. Epub 2024 May 30.
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.
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.
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 ( = 0.044) but a significant positive association with the psychotic/irritable mania dimension ( = 0.001). PRS of EA major depressive disorder demonstrated a significant negative association with the elation dimension ( = 0.003) but a significant positive association with the comorbidity dimension ( = 0.028).
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.
双相情感障碍（BD）在横断面和纵向研究中均表现出异质性的疾病表现。这种表型异质性可能反映了潜在的遗传异质性。同时，在临床和生物标志物水平上观察到BD与其他精神疾病之间存在重叠特征，这意味着它们之间存在共同的生物学机制。本研究将这两个问题纳入单一研究设计中，调查BD表型异质性亚型是否与其他精神疾病具有独特的多基因基础。
我们先前研究中确定的BD的六个终生表型维度用作目标表型。分析了这些表型维度与东亚（EA）和其他可用人群中主要精神疾病的多基因风险评分（PRSs）之间的关联。
每个表型维度与精神疾病的PRSs显示出不同的关联模式。EA精神分裂症的PRS与循环性维度呈显著负相关（ = 0.044），但与精神病性/易激惹躁狂维度呈显著正相关（ = 0.001）。EA重度抑郁症的PRS与欣快维度呈显著负相关（ = 0.003），但与共病维度呈显著正相关（ = 0.028）。
本研究表明，BD中基于终生的明确定义的表型维度与其他主要精神疾病具有不同的遗传风险。这一发现支持了BD中的遗传异质性，并表明BD亚型与BD以外的其他精神障碍之间存在多效性。有必要在 ancestrally diverse populations中对精神疾病进行深度表型分析的进一步基因组分析，以阐明精神病学中的诊断内异质性和诊断间共性问题。
