Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans.
Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans.
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DOI：
10.1038/s41467-022-28276-x
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发表时间：
2022-02-14
影响因子：
16.6
通讯作者：
H3Africa Consortium
中科院分区：
文献类型：
--
作者：
Boua PR;Brandenburg JT;Choudhury A;Sorgho H;Nonterah EA;Agongo G;Asiki G;Micklesfield L;Choma S;Gómez-Olivé FX;Hazelhurst S;Tinto H;Crowther NJ;Mathew CG;Ramsay M;AWI-Gen Study;H3Africa Consortium
动脉粥样硬化先于心血管疾病(CVD)的临床表现出现。我们使用颈动脉内中膜厚度(CIMT)研究了居住在撒哈拉以南非洲四个国家的7894名无关成年人(女性3963名，男性3931名；年龄40至60岁)对动脉粥样硬化的遗传易感性。超声检测CIMT，H3Africa SNP芯片进行基因分型。发现了两个新的非洲特有的Mean-max CIMT基因座，SIRPA(p = 4.7E-08)和FBXL17(p = 2.5E-08)。性别分层分析显示，SNX29(p = 6.3E-09)是男性特有的基因座，而LARP6(p = 2.4E-09)和PROK1(p = 1.0E-08)是女性特有的基因座。我们复制了以前CIMT与不同铅SNPs的关联，这些SNPs与最初在欧洲人群中发现的SNPs连锁不平衡。我们的研究发现，从女性特有的信号中，参与雌激素反应的基因显著丰富。已确定的基因与动脉粥样硬化和/或心血管疾病、性别差异和来自非非洲研究的信号的可转移性具有生物学相关性。对疾病相关性状的遗传研究大多是在欧洲人群中进行的。在这里，作者在撒哈拉以南非洲的样本中进行了一项关于颈动脉内膜-中层厚度的全基因组关联研究，找到了人群特定和性别特定的基因座。
Atherosclerosis precedes the onset of clinical manifestations of cardiovascular diseases (CVDs). We used carotid intima-media thickness (cIMT) to investigate genetic susceptibility to atherosclerosis in 7894 unrelated adults (3963 women, 3931 men; 40 to 60 years) resident in four sub-Saharan African countries. cIMT was measured by ultrasound and genotyping was performed on the H3Africa SNP Array. Two new African-specific genome-wide significant loci for mean-max cIMT, SIRPA (p = 4.7E-08), and FBXL17 (p = 2.5E-08), were identified. Sex-stratified analysis revealed associations with one male-specific locus, SNX29 (p = 6.3E-09), and two female-specific loci, LARP6 (p = 2.4E-09) and PROK1 (p = 1.0E-08). We replicate previous cIMT associations with different lead SNPs in linkage disequilibrium with SNPs primarily identified in European populations. Our study find significant enrichment for genes involved in oestrogen response from female-specific signals. The genes identified show biological relevance to atherosclerosis and/or CVDs, sex-differences and transferability of signals from non-African studies. Genetic studies of disease-relevant traits have mostly been performed on European populations. Here, the authors perform a genome-wide association study for carotid intima-media thickness, in sub-Saharan African samples, finding population-specific and sex-specific loci.
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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：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
56.9
作者：
Hinds, DA;Stuve, LL;Cox, DR
通讯作者：
Cox, DR
影响因子：
7.7
作者：
Derra, Karim;Rouamba, Eli;Tinto, Halidou
通讯作者：
Tinto, Halidou