Background and Hypothesis While genetic correlations, pleiotropic loci, and shared genetic mechanisms of psychiatric disorders have been extensively studied in European populations, the investigation of these factors in East Asian populations has been relatively limited. Study Design To identify novel pleiotropic risk loci for depression and schizophrenia (SCZ) in East Asians. We utilized the most comprehensive dataset available for East Asians and quantified the genetic overlap between depression, SCZ, and their related traits via a multitrait genome-wide association study. Global and local genetic correlations were estimated by LDSC and ρ-HESS. Pleiotropic loci were identified by the multitrait analysis of GWAS (MTAG). Study Results Besides the significant correlation between depression and SCZ, our analysis revealed genetic correlations between depression and obesity-related traits, such as weight, BMI, T2D, and HDL. In SCZ, significant correlations were detected with HDL, heart diseases and use of various medications. Conventional meta-analysis of depression and SCZ identified a novel locus at 1q25.2 in East Asians. Further multitrait analysis of depression, SCZ and related traits identified ten novel pleiotropic loci for depression, and four for SCZ. Conclusions Our findings demonstrate shared genetic underpinnings between depression and SCZ in East Asians, as well as their associated traits, providing novel candidate genes for the identification and prioritization of therapeutic targets specific to this population.

中文翻译：

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多性状遗传分析确定了东亚人抑郁症和精神分裂症的新多效性基因座


背景和假设虽然欧洲人群中精神疾病的遗传相关性、多效性基因座和共有遗传机制已得到广泛研究，但对东亚人群中这些因素的研究相对有限。研究设计旨在确定东亚人抑郁症和精神分裂症 (SCZ) 的新多效性风险位点。我们利用了东亚人可用的最全面的数据集，并通过多性状全基因组关联研究量化了抑郁症、SCZ 及其相关性状之间的遗传重叠。通过 LDSC 和 ρ-HESS 估计全局和局部遗传相关性。通过 GWAS (MTAG) 多性状分析鉴定多效性基因座。研究结果 除了抑郁症与 SCZ 之间存在显着相关性外，我们的分析还揭示了抑郁症与肥胖相关特征（如体重、BMI、T2D 和 HDL）之间的遗传相关性。在 SCZ 中，检测到与 HDL、心脏病和各种药物的使用存在显着相关性。抑郁症和 SCZ 的传统荟萃分析在东亚人中发现了 1q25.2 的一个新基因座。对抑郁症、SCZ 和相关性状的进一步多性状分析确定了 10 个新的抑郁症多效性基因座和 4 个 SCZ 基因座。结论 我们的研究结果证明了东亚人抑郁症和 SCZ 之间的共同遗传基础及其相关特征，为识别和优先考虑针对该人群的治疗靶点提供了新的候选基因。