Transcriptome-wide association study of HIV-1 acquisition identifies HERC1 as a susceptibility gene.
Transcriptome-wide association study of HIV-1 acquisition identifies HERC1 as a susceptibility gene.
复制标题
DOI：
10.1016/j.isci.2022.104854
复制
发表时间：
2022-09-16
期刊：
影响因子：
5.8
通讯作者：
Powell, Timothy R.
中科院分区：
文献类型：
--
作者：
Duarte, Rodrigo R. R.;Pain, Oliver;Furler, Robert L.;Nixon, Douglas F.;Powell, Timothy R.
能够防止 1 型 HIV (HIV-1) 感染的宿主遗传因素仍然难以捉摸，特别是常见遗传变异的贡献。在这里，我们对 HIV-1 获取进行了最大的全基因组关联荟萃分析，其中包括 7,303 名 HIV-1 阳性个体和 587,343 名人群对照。我们鉴定了 25 个具有暗示关联的独立遗传基因座，其中一个在主要组织相容性复合体 (MHC) 基因座内具有全基因组显着性。排除 MHC 信号后，连锁不平衡评分回归分析显示 SNP 遗传力为 21%，并且与行为因素存在遗传相关性。一项全转录组关联研究确定了 15 个易感基因，包括 HERC1、UEVLD 和 HIST1H4K。来自条件分析和精细绘图的综合证据表明，免疫细胞中的 HERC1 下调是与 HIV-1 获得相关的强大机制。对 HERC1 和其他已确定候选者的功能研究，以及更大规模的基因研究，有可能进一步加深我们对与 HIV-1 保护相关的宿主机制的理解。 HIV-1 获得具有高度多基因性，SNP 遗传力估计为 21% HIV-1 获得与吸烟等行为因素相关 免疫细胞中 HERC1 下调与 HIV-1 获得风险相关 遗传学；免疫;生物信息学
The host genetic factors conferring protection against HIV type 1 (HIV-1) acquisition remain elusive, and in particular the contributions of common genetic variants. Here, we performed the largest genome-wide association meta-analysis of HIV-1 acquisition, which included 7,303 HIV-1-positive individuals and 587,343 population controls. We identified 25 independent genetic loci with suggestive association, of which one was genome-wide significant within the major histocompatibility complex (MHC) locus. After exclusion of the MHC signal, linkage disequilibrium score regression analyses revealed a SNP heritability of 21% and genetic correlations with behavioral factors. A transcriptome-wide association study identified 15 susceptibility genes, including HERC1, UEVLD, and HIST1H4K. Convergent evidence from conditional analyses and fine-mapping identified HERC1 downregulation in immune cells as a robust mechanism associated with HIV-1 acquisition. Functional studies on HERC1 and other identified candidates, as well as larger genetic studies, have the potential to further our understanding of the host mechanisms associated with protection against HIV-1. HIV-1 acquisition is highly polygenic, with a SNP heritability estimate of 21% HIV-1 acquisition correlates with behavioral factors such as smoking HERC1 downregulation in immune cells is associated with HIV-1 acquisition risk Genetics; Immunity; Bioinformatics
登录
查看更多内容
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
4.5
作者：
Feng H;Mancuso N;Gusev A;Majumdar A;Major M;Pasaniuc B;Kraft P
通讯作者：
Kraft P
DOI：
10.1192/bjp.bp.115.168229
发表时间：
2016-09
期刊：
The British journal of psychiatry : the journal of mental science
影响因子：
--
作者：
Coleman JR;Lester KJ;Keers R;Roberts S;Curtis C;Arendt K;Bögels S;Cooper P;Creswell C;Dalgleish T;Hartman CA;Heiervang ER;Hötzel K;Hudson JL;In-Albon T;Lavallee K;Lyneham HJ;Marin CE;Meiser-Stedman R;Morris T;Nauta MH;Rapee RM;Schneider S;Schneider SC;Silverman WK;Thastum M;Thirlwall K;Waite P;Wergeland GJ;Breen G;Eley TC
通讯作者：
Eley TC
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
10.6
作者：
Dall'Aglio L;Lewis CM;Pain O
通讯作者：
Pain O