在 125000 名非洲裔个体中进行多特征发现和脂质基因座的精细定位。
Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry.
机构信息
The African Computational Genomic (TACG) Research Group, MRC/UVRI and LSHTM, Entebbe, Uganda.
Malawi Epidemiology and Intervention Research Unit, Lilongwe, Malawi.
出版信息
Nat Commun. 2023 Sep 5;14(1):5403. doi: 10.1038/s41467-023-41271-0.
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.
大多数脂质特征的全基因组关联研究（GWAS）都侧重于对脂质特征的单独分析。此外，评估非洲血统人群中与多种脂质特征相关的遗传变异的 GWAS 非常有限。为了进一步鉴定和定位对脂质特征具有多效性影响的基因座，我们在 125000 名非洲血统个体中进行了全基因组荟萃分析、GWAS 的多特征分析（MTAG）和多特征精细映射（flashfm）。我们的荟萃分析和 MTAG 分别确定了四个和 14 个与脂质特征相关的新基因座。与单特征精细映射的 JAM 相比，flashfm 使 99%可信区间的平均大小减少了 18%。此外，与 JAM 相比，我们用 flashfm 鉴定出了更多具有因果关系后验概率>0.9 的遗传变异。总之，我们发现了与脂质特征相关的更多新基因座，并且 flashfm 缩小了 99%的可信区间大小，以鉴定与非洲血统多种脂质特征相关的因果遗传变异。
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