自杀想法和行为的全基因组关联研究:精神科基因组学联盟自杀问题工作组的最新报告

IF 6.1 2区 医学 Q1 CLINICAL NEUROLOGY European Neuropsychopharmacology Pub Date : 2024-10-01 DOI:10.1016/j.euroneuro.2024.08.049
Sarah Colbert , The Suicide Working Group of the Psychiatric Genomics Consortium , Douglas Ruderfer , Anna Docherty , Niamh Mullins
{"title":"自杀想法和行为的全基因组关联研究:精神科基因组学联盟自杀问题工作组的最新报告","authors":"Sarah Colbert ,&nbsp;The Suicide Working Group of the Psychiatric Genomics Consortium ,&nbsp;Douglas Ruderfer ,&nbsp;Anna Docherty ,&nbsp;Niamh Mullins","doi":"10.1016/j.euroneuro.2024.08.049","DOIUrl":null,"url":null,"abstract":"<div><div>Suicidal thoughts and behaviors, specifically suicidal ideation (SI), suicide attempt (SA) and suicide death (SD), are substantially heritable, with twin and family studies estimating heritabilities in the range of 30-55%. Recently, genome-wide association studies (GWAS) have reached sufficient sample sizes to conduct well-powered analyses, leading to the identification of 4, 12 and 2 loci associated with SI, SA, and SD, respectively. Importantly, these phenotypes show strong, yet incomplete, genetic correlations with each other, motivating genetic studies of each phenotype separately to understand their underlying biology and the progression from one to the next. Here, we present an update on the progress of the latest and most extensive GWAS of SI, SA, and SD, conducted by the Psychiatric Genomics Consortium Suicide Working Group (PGC SUI).</div><div><strong>Methods:</strong> Data comprise 30 cohorts contributing to the SI GWAS (N cases=256,257, N controls=1,298,106), 42 cohorts contributing to the SA GWAS (N cases=73,087, N controls=1,327,350), and 6 cohorts contributing to the SD GWAS (N cases=6,775, N controls=841,216). Notably, these cohorts comprise individuals from four diverse genetic ancestry groups: admixed European ancestries (EUR), admixed African ancestries (AA), East Asian ancestries (EA) and admixed Latino ancestries (LAT). New phenotyping and analytic protocols have been developed by PGC SUI to ensure exceptional rigor and comparability across cohorts. GWAS meta-analyses will be conducted via inverse variance-weighted fixed effects models to identify novel genetic risk loci. Post-GWAS analyses include pathway, tissue and drug target enrichment, and examination of the SNP-heritabilities (h2SNP), and genetic relationships between SI, SA, and SD.</div><div>Preliminary analysis using the currently available SA data (SA cases = 47,174, controls = 941,010 from 26 cohorts) yielded a h2SNP of 5.6% (se = 0.003, p = 1.2e-68) and ten replicated and three novel genome-wide significant (GWS) loci, containing FYN, AIG1, and DCC. Eight GWS loci were identified in the EUR meta-analysis (h2SNP = 7%, se = 0.004) which replicated previous findings. No GWS loci were identified in the AA (h2SNP = 9.8%, se = 0.02), EA (h2SNP 5.1%, se = 0.04) or LAT (h2SNP = 10%, se =0.07) GWAS meta-analyses. We also identified significant enrichment in genes expressed in several brain tissues from GTEx and summary data-based Mendelian Randomization revealed two novel genes (GMPPB, FURIN) significantly associated with SA. This SA GWAS showed significant genetic correlations with published GWAS of SI (rg = 0.80, se = 0.04), SD (rg = 0.77, se = 0.05), and several psychiatric disorders (rgs = 0.26-0.70).</div><div>Additional data intake is almost complete within PGC SUI, and this presentation will share the final GWAS results and novel biological insights. Increased sample sizes in combination with streamlined protocols for phenotyping and analyzing suicidal thoughts and behaviors are yielding powerful genetic studies of SI, SA, and SD. Results from this study will characterize the genetic contributions to suicidal thoughts and behaviors and provide insights into their underlying biological mechanisms.</div></div>","PeriodicalId":12049,"journal":{"name":"European Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":6.1000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"GENOME-WIDE ASSOCIATION STUDIES OF SUICIDAL THOUGHTS AND BEHAVIORS: AN UPDATE FROM THE PSYCHIATRIC GENOMICS CONSORTIUM SUICIDE WORKING GROUP\",\"authors\":\"Sarah Colbert ,&nbsp;The Suicide Working Group of the Psychiatric Genomics Consortium ,&nbsp;Douglas Ruderfer ,&nbsp;Anna Docherty ,&nbsp;Niamh Mullins\",\"doi\":\"10.1016/j.euroneuro.2024.08.049\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Suicidal thoughts and behaviors, specifically suicidal ideation (SI), suicide attempt (SA) and suicide death (SD), are substantially heritable, with twin and family studies estimating heritabilities in the range of 30-55%. Recently, genome-wide association studies (GWAS) have reached sufficient sample sizes to conduct well-powered analyses, leading to the identification of 4, 12 and 2 loci associated with SI, SA, and SD, respectively. Importantly, these phenotypes show strong, yet incomplete, genetic correlations with each other, motivating genetic studies of each phenotype separately to understand their underlying biology and the progression from one to the next. Here, we present an update on the progress of the latest and most extensive GWAS of SI, SA, and SD, conducted by the Psychiatric Genomics Consortium Suicide Working Group (PGC SUI).</div><div><strong>Methods:</strong> Data comprise 30 cohorts contributing to the SI GWAS (N cases=256,257, N controls=1,298,106), 42 cohorts contributing to the SA GWAS (N cases=73,087, N controls=1,327,350), and 6 cohorts contributing to the SD GWAS (N cases=6,775, N controls=841,216). Notably, these cohorts comprise individuals from four diverse genetic ancestry groups: admixed European ancestries (EUR), admixed African ancestries (AA), East Asian ancestries (EA) and admixed Latino ancestries (LAT). New phenotyping and analytic protocols have been developed by PGC SUI to ensure exceptional rigor and comparability across cohorts. GWAS meta-analyses will be conducted via inverse variance-weighted fixed effects models to identify novel genetic risk loci. Post-GWAS analyses include pathway, tissue and drug target enrichment, and examination of the SNP-heritabilities (h2SNP), and genetic relationships between SI, SA, and SD.</div><div>Preliminary analysis using the currently available SA data (SA cases = 47,174, controls = 941,010 from 26 cohorts) yielded a h2SNP of 5.6% (se = 0.003, p = 1.2e-68) and ten replicated and three novel genome-wide significant (GWS) loci, containing FYN, AIG1, and DCC. Eight GWS loci were identified in the EUR meta-analysis (h2SNP = 7%, se = 0.004) which replicated previous findings. No GWS loci were identified in the AA (h2SNP = 9.8%, se = 0.02), EA (h2SNP 5.1%, se = 0.04) or LAT (h2SNP = 10%, se =0.07) GWAS meta-analyses. We also identified significant enrichment in genes expressed in several brain tissues from GTEx and summary data-based Mendelian Randomization revealed two novel genes (GMPPB, FURIN) significantly associated with SA. This SA GWAS showed significant genetic correlations with published GWAS of SI (rg = 0.80, se = 0.04), SD (rg = 0.77, se = 0.05), and several psychiatric disorders (rgs = 0.26-0.70).</div><div>Additional data intake is almost complete within PGC SUI, and this presentation will share the final GWAS results and novel biological insights. Increased sample sizes in combination with streamlined protocols for phenotyping and analyzing suicidal thoughts and behaviors are yielding powerful genetic studies of SI, SA, and SD. Results from this study will characterize the genetic contributions to suicidal thoughts and behaviors and provide insights into their underlying biological mechanisms.</div></div>\",\"PeriodicalId\":12049,\"journal\":{\"name\":\"European Neuropsychopharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Neuropsychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0924977X24002487\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Neuropsychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0924977X24002487","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

自杀想法和行为,特别是自杀意念(SI)、自杀未遂(SA)和自杀死亡(SD),具有很强的遗传性,双胞胎和家族研究估计其遗传率在 30-55% 之间。最近,全基因组关联研究(GWAS)已经达到了足够的样本量,可以进行强效分析,从而发现了分别与 SI、SA 和 SD 相关的 4、12 和 2 个基因位点。重要的是,这些表型之间显示出很强但不完全的遗传相关性,这促使我们对每种表型分别进行遗传研究,以了解其潜在的生物学特性以及从一种表型到下一种表型的发展过程。在此,我们将介绍精神病基因组学联盟自杀工作组(PGC SUI)对 SI、SA 和 SD 进行的最新、最广泛的 GWAS 研究的最新进展:数据包括参与 SI 基因组研究的 30 个队列(病例数=256,257,对照数=1,298,106),参与 SA 基因组研究的 42 个队列(病例数=73,087,对照数=1,327,350),以及参与 SD 基因组研究的 6 个队列(病例数=6,775,对照数=841,216)。值得注意的是,这些队列包括来自四个不同基因血统群体的个体:混血欧洲血统(EUR)、混血非洲血统(AA)、混血东亚血统(EA)和混血拉丁血统(LAT)。PGC SUI 已经制定了新的表型和分析协议,以确保不同队列之间具有卓越的严谨性和可比性。将通过反方差加权固定效应模型进行 GWAS 元分析,以确定新的遗传风险位点。GWAS 后分析包括途径、组织和药物靶点富集,以及 SNP 遗传性(h2SNP)检查和 SI、SA 和 SD 之间的遗传关系。利用目前可用的 SA 数据(来自 26 个队列的 SA 病例 = 47,174 例,对照 = 941,010 例)进行的初步分析发现,h2SNP 为 5.6%(se = 0.003,p = 1.2e-68),有 10 个重复的和 3 个新的全基因组显著(GWS)位点,包括 FYN、AIG1 和 DCC。在欧洲荟萃分析(h2SNP = 7%,se = 0.004)中确定了 8 个 GWS 位点,这些位点重复了之前的研究结果。在 AA(h2SNP = 9.8%,se = 0.02)、EA(h2SNP 5.1%,se = 0.04)或 LAT(h2SNP = 10%,se = 0.07)GWAS 元分析中未发现 GWS 位点。我们还从 GTEx 中发现了一些脑组织中表达基因的明显富集,基于数据的孟德尔随机化总结发现了两个与 SA 显著相关的新基因(GMPPB 和 FURIN)。该SA GWAS与已发表的SI(rg = 0.80,se = 0.04)、SD(rg = 0.77,se = 0.05)和几种精神疾病(rgs = 0.26-0.70)的GWAS有明显的遗传相关性。样本量的增加与表型和分析自杀想法和行为的简化方案相结合,正在对SI、SA和SD进行强有力的遗传研究。这项研究的结果将描述自杀想法和行为的遗传贡献,并提供对其潜在生物学机制的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
GENOME-WIDE ASSOCIATION STUDIES OF SUICIDAL THOUGHTS AND BEHAVIORS: AN UPDATE FROM THE PSYCHIATRIC GENOMICS CONSORTIUM SUICIDE WORKING GROUP
Suicidal thoughts and behaviors, specifically suicidal ideation (SI), suicide attempt (SA) and suicide death (SD), are substantially heritable, with twin and family studies estimating heritabilities in the range of 30-55%. Recently, genome-wide association studies (GWAS) have reached sufficient sample sizes to conduct well-powered analyses, leading to the identification of 4, 12 and 2 loci associated with SI, SA, and SD, respectively. Importantly, these phenotypes show strong, yet incomplete, genetic correlations with each other, motivating genetic studies of each phenotype separately to understand their underlying biology and the progression from one to the next. Here, we present an update on the progress of the latest and most extensive GWAS of SI, SA, and SD, conducted by the Psychiatric Genomics Consortium Suicide Working Group (PGC SUI).
Methods: Data comprise 30 cohorts contributing to the SI GWAS (N cases=256,257, N controls=1,298,106), 42 cohorts contributing to the SA GWAS (N cases=73,087, N controls=1,327,350), and 6 cohorts contributing to the SD GWAS (N cases=6,775, N controls=841,216). Notably, these cohorts comprise individuals from four diverse genetic ancestry groups: admixed European ancestries (EUR), admixed African ancestries (AA), East Asian ancestries (EA) and admixed Latino ancestries (LAT). New phenotyping and analytic protocols have been developed by PGC SUI to ensure exceptional rigor and comparability across cohorts. GWAS meta-analyses will be conducted via inverse variance-weighted fixed effects models to identify novel genetic risk loci. Post-GWAS analyses include pathway, tissue and drug target enrichment, and examination of the SNP-heritabilities (h2SNP), and genetic relationships between SI, SA, and SD.
Preliminary analysis using the currently available SA data (SA cases = 47,174, controls = 941,010 from 26 cohorts) yielded a h2SNP of 5.6% (se = 0.003, p = 1.2e-68) and ten replicated and three novel genome-wide significant (GWS) loci, containing FYN, AIG1, and DCC. Eight GWS loci were identified in the EUR meta-analysis (h2SNP = 7%, se = 0.004) which replicated previous findings. No GWS loci were identified in the AA (h2SNP = 9.8%, se = 0.02), EA (h2SNP 5.1%, se = 0.04) or LAT (h2SNP = 10%, se =0.07) GWAS meta-analyses. We also identified significant enrichment in genes expressed in several brain tissues from GTEx and summary data-based Mendelian Randomization revealed two novel genes (GMPPB, FURIN) significantly associated with SA. This SA GWAS showed significant genetic correlations with published GWAS of SI (rg = 0.80, se = 0.04), SD (rg = 0.77, se = 0.05), and several psychiatric disorders (rgs = 0.26-0.70).
Additional data intake is almost complete within PGC SUI, and this presentation will share the final GWAS results and novel biological insights. Increased sample sizes in combination with streamlined protocols for phenotyping and analyzing suicidal thoughts and behaviors are yielding powerful genetic studies of SI, SA, and SD. Results from this study will characterize the genetic contributions to suicidal thoughts and behaviors and provide insights into their underlying biological mechanisms.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
European Neuropsychopharmacology
European Neuropsychopharmacology 医学-精神病学
CiteScore
10.30
自引率
5.40%
发文量
730
审稿时长
41 days
期刊介绍: European Neuropsychopharmacology is the official publication of the European College of Neuropsychopharmacology (ECNP). In accordance with the mission of the College, the journal focuses on clinical and basic science contributions that advance our understanding of brain function and human behaviour and enable translation into improved treatments and enhanced public health impact in psychiatry. Recent years have been characterized by exciting advances in basic knowledge and available experimental techniques in neuroscience and genomics. However, clinical translation of these findings has not been as rapid. The journal aims to narrow this gap by promoting findings that are expected to have a major impact on both our understanding of the biological bases of mental disorders and the development and improvement of treatments, ideally paving the way for prevention and recovery.
期刊最新文献
Placental epigenetic signatures of maternal distress in glucocorticoid-related genes and newborn outcomes: A study of Spanish primiparous women The microRNA profile of brain-derived extracellular vesicles: A promising step forward in developing pharmacodynamic biomarkers for psychiatric disorders A meta-analysis of data-driven cognitive subgroups in bipolar disorder “The role of gut microbiota in adult attention deficit hyperactivity disorder: Insights and implications” Lurasidone-related adverse events: A comprehensive analysis from the FAERs database in real-world settings
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1