GWAS identifies genetic clusters of cardiometabolic risk factors in continental Africans

Abstract Cardiometabolic risk factors (CMRFs) are a growing global health concern. Here, we set out to identify novel genetic loci associated with CMRFs in two continental African populations, Ugandans and South African Zulu’s. Thus, we conducted a multivariate meta-analysis with META-SCOPA; where six CMRFs comprising of waist circumference (WC), triglycerides (TG), high-density lipoprotein (HDL), systolic blood pressure (SBP), diastolic blood pressure (DBP), and glycated hemoglobin A1c (HbA1c) were used. META-SCOPA identified five novel loci and its Multi-marker Analysis of GenoMic Annotation (MAGMA) gene-set analysis showed an association with human histone acetyltransferase/male sex-lethal (MSL) complex. Fine-mapping, colocalization, tissue expression analyses, and phenome-wide association study (PheWAS) were also implemented to better understand the meta-analysis findings. Furthermore, as a supplement a principal component analysis (PCA) GWAS was also performed on the same six CMRFs. The first principal component denoted cardiometabolic_PC1 was driven mostly by DBP and SBP. Five novel, significant loci were identified after the meta-analysis. Ultimately, our novel loci and gene-sets offer fresh insights into the clustering of CMRFs and propose a unique link to the human histone acetyltransferase/MSL complex, as well as circulatory system processes in continental Africans. Additional large-scale efforts in Africa are needed to understand the clustering of CMRFs.