Identifying tagging SNPs for African specific genetic variation from the African Diaspora Genome

Abstract

A primary goal of The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to develop an 'African Diaspora Power Chip' (ADPC), a genotyping array consisting of tagging SNPs, useful in comprehensively identifying African specific genetic variation. This array is designed based on the novel variation identified in 642 CAAPA samples of African ancestry with high coverage whole genome sequence data (~30× depth). This novel variation extends the pattern of variation catalogued in the 1000 Genomes and Exome Sequencing Projects to a spectrum of populations representing the wide range of West African genomic diversity. These individuals from CAAPA also comprise a large swath of the African Diaspora population and incorporate historical genetic diversity covering nearly the entire Atlantic coast of the Americas. Here we show the results of designing and producing such a microchip array. This novel array covers African specific variation far better than other commercially available arrays, and will enable better GWAS analyses for researchers with individuals of African descent in their study populations. A recent study cataloging variation in continental African populations suggests this type of African-specific genotyping array is both necessary and valuable for facilitating large-scale GWAS in populations of African ancestry.

Figure 1. The ADPC design pipeline, describing the steps taken to whittle ~15 million novel African SNPs into a 627k African-targeted GWAS array.

Figure 2. Estimated imputation coverage of variants tagged by the ADPC content as part of the MEGA array.

(a) Coverage in 1000 Genomes African populations is >=0.8 r² down to 1% MAF. (b) Coverage in 1000 Genomes admixed African populations is >=0.8 r² down to 1% MAF

Figure 3. Projected minor allele frequency histograms for the ADPC and OmniExpress arrays overlayed with one another.

The disparity between the arrays is significant, and represents very different tagging approaches. This makes them well suited to complement each other.