A different view on fine-scale population structure in Western African populations

Abstract

Due to its long genetic evolutionary history, Africans exhibit more genetic variation than any other population in the world. Their genetic diversity further lends itself to subdivisions of Africans into groups of individuals with a genetic similarity of varying degrees of granularity. It remains challenging to detect fine-scale structure in a computationally efficient and meaningful way. In this paper, we present a proof-of-concept of a novel fine-scale population structure detection tool with Western African samples. These samples consist of 1396 individuals from 25 ethnic groups (two groups are African American descendants). The strategy is based on a recently developed tool called IPCAPS. IPCAPS, or Iterative Pruning to CApture Population Structure, is a genetic divisive clustering strategy that enhances iterative pruning PCA, is robust to outliers and does not require a priori computation of haplotypes. Our strategy identified in total 12 groups and 6 groups were revealed as fine-scale structure detected in the samples from Cameroon, Gambia, Mali, Southwest USA, and Barbados. Our finding helped to explain evolutionary processes in the analyzed West African samples and raise awareness for fine-scale structure resolution when conducting genome-wide association and interaction studies.

Evolutionary history of sickle-cell mutation: implications for global genetic medicine

“…Indeed, as Haldane noted, only a small gain in fitness would be required for a variant to attain its equilibrium frequency ( 8 ). The strongest SCT protective effect has now been recorded in West African (Gambia), whereas the weakest effect was recorded in Cameroon, although it is unclear whether fine-scale genetic sub-structure in Cameroon may have confounded these analyses ( 11 , 12 ).…”

Alternative Applications of Genotyping Array Data Using Multivariant Methods

“…IBD-based methods are only useful for very recent population developments. Another study [12] used a very different method of iteratively pruned Principal Component Analysis to investigate the much older population structure of West Africa.…”

Harmine and 7,8-dihydroxyflavone synergistically suitable for amyotrophic lateral sclerosis management: An in silico study

“…Identification of genes underlying ALS has provided critical insights into the cellular mechanisms leading to neurodegeneration, such as protein homeostasis, cytoskeleton alterations, RNA metabolism, endoplasmic reticulum stress, nucleocytoplasmic transport, and autophagy defects (Saez-Atienzar et al 2021). The genome-wide association study of Western African populations reported that 46 genes out of 165 genes were linked to sporadic ALS in the population (Chaichoompu et al 2020). A recent study that systematically applied a polygenic risk score analysis to a genomic dataset involving 78,500 individuals to distinguish the cellular processes driving ALS, has reported six differentially expressed genes (ATG16L2, ACSL5, MAP1LC3A, MAPKAPK3, PLXNB2, and SCFD1) within the significant pathways that are relevant to ALS (Saez-Atienzar et al 2021).…”