Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry.

Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry.
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DOI:
10.1038/s41467-023-41271-0
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发表时间:
2023-09-05
影响因子:
16.6
通讯作者:
Fatumo, Segun
Fatumo, Segun
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kamiza, Abram Bunya;Toure, Sounkou M.;Zhou, Feng;Soremekun, Opeyemi;Cisse, Cheickna;Wele, Mamadou;Toure, Aboubacrine M.;Nashiru, Oyekanmi;Corpas, Manuel;Nyirenda, Moffat;Crampin, Amelia;Shaffer, Jeffrey;Doumbia, Seydou;Zeggini, Eleftheria;Morris, Andrew P.;Asimit, Jennifer L.;Chikowore, Tinashe;Fatumo, Segun

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大多数关于脂类性状的全基因组关联研究(GWAS)集中在对脂类性状的单独分析上。此外,评估与非洲血统中多种血脂性状相关的遗传变异的GWAS有限。为了进一步识别和定位对血脂性状具有多效性效应的基因座,我们对125,000名非洲血统的个体进行了全基因组荟萃分析、多性状分析(MTAG)和多性状精细定位(Flashfm)。我们的荟萃分析和MTAG分别确定了4个和14个新的与血脂性状相关的基因座。与JAM的单性状精细定位相比,Flashfm的99%可信集合大小平均减少了18%。此外,我们确定了更多的遗传变异与后验概率的因果关系>0.9与flashfm比果酱。总之,我们发现了更多与血脂性状相关的新基因座,Flashfm减少了99%的可信集合大小,以确定与非洲血统中多种血脂性状相关的因果遗传变异。很少有全基因组的关联研究同时分析多种血脂性状,特别是在非洲血统的个体中。为了解决这一问题,作者对非洲血统的个体进行了多性状分析和精细定位,以寻找与血脂性状相关的新的遗传位点。
Most genome-wide association studies (GWAS) for lipid traits focus on the separate analysis of lipid traits. Moreover, there are limited GWASs evaluating the genetic variants associated with multiple lipid traits in African ancestry. To further identify and localize loci with pleiotropic effects on lipid traits, we conducted a genome-wide meta-analysis, multi-trait analysis of GWAS (MTAG), and multi-trait fine-mapping (flashfm) in 125,000 individuals of African ancestry. Our meta-analysis and MTAG identified four and 14 novel loci associated with lipid traits, respectively. flashfm yielded an 18% mean reduction in the 99% credible set size compared to single-trait fine-mapping with JAM. Moreover, we identified more genetic variants with a posterior probability of causality >0.9 with flashfm than with JAM. In conclusion, we identified additional novel loci associated with lipid traits, and flashfm reduced the 99% credible set size to identify causal genetic variants associated with multiple lipid traits in African ancestry. There have been few genome-wide association studies that analyze multiple lipid traits simultaneously, especially in individuals of African ancestry. To address this, the authors performed a multi-trait analysis of GWAS along with fine-mapping to find new genetic loci associated with lipid traits in individuals of African ancestry.
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