Multitrait Genetic Analysis Identifies Novel Pleiotropic Loci for Depression and Schizophrenia in East Asians.

IF 5.3 1区医学 Q1 PSYCHIATRY Schizophrenia Bulletin Pub Date : 2024-08-27 DOI:10.1093/schbul/sbae145

Yingchao Song, Linzehao Li, Yue Jiang, Bichen Peng, Hengxuan Jiang, Zhen Chao, Xiao Chang

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Abstract

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.

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多特征遗传分析发现了东亚人抑郁和精神分裂症的新型多效基因位点

背景与假设：虽然在欧洲人群中对精神疾病的遗传相关性、多向位点和共同遗传机制进行了广泛研究，但在东亚人群中对这些因素的研究却相对有限：研究设计：确定东亚人患抑郁症和精神分裂症（SCZ）的新的多向性风险基因位点。我们利用现有最全面的东亚人数据集，通过多特征全基因组关联研究量化了抑郁症、精神分裂症及其相关性状之间的遗传重叠。通过LDSC和ρ-HESS估算了整体和局部遗传相关性。多特征全基因组关联分析（MTAG）确定了多效应位点：研究结果：除了抑郁症与SCZ之间的显着相关性外，我们的分析还揭示了抑郁症与肥胖相关性状（如体重、体重指数、T2D和高密度脂蛋白）之间的遗传相关性。在 SCZ 中，我们发现抑郁症与高密度脂蛋白、心脏病和服用各种药物有明显的相关性。对抑郁症和SCZ的常规荟萃分析在东亚人中发现了一个位于1q25.2的新基因座。对抑郁症、SCZ和相关性状的进一步多性状分析发现了抑郁症的10个新的多效应基因位点和SCZ的4个新的多效应基因位点：我们的研究结果表明，东亚人的抑郁症和SCZ及其相关性状之间存在共同的遗传基础，这为确定该人群的治疗目标和优先顺序提供了新的候选基因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Schizophrenia Bulletin 医学-精神病学

CiteScore

11.40

自引率

6.10%

发文量

163

审稿时长

4-8 weeks

期刊介绍： Schizophrenia Bulletin seeks to review recent developments and empirically based hypotheses regarding the etiology and treatment of schizophrenia. We view the field as broad and deep, and will publish new knowledge ranging from the molecular basis to social and cultural factors. We will give new emphasis to translational reports which simultaneously highlight basic neurobiological mechanisms and clinical manifestations. Some of the Bulletin content is invited as special features or manuscripts organized as a theme by special guest editors. Most pages of the Bulletin are devoted to unsolicited manuscripts of high quality that report original data or where we can provide a special venue for a major study or workshop report. Supplement issues are sometimes provided for manuscripts reporting from a recent conference.