Comparison of genome-wide variation between Malawians and African ancestry HapMap populations

• Published in: Journal of human genetics Vol. 55; no. 6; pp. 366 - 374
• Main Authors: Joubert, Bonnie R, North, Kari E, Wang, Yunfei, Mwapasa, Victor, Franceschini, Nora, Meshnick, Steven R, Lange, Ethan M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2010; Nature Publishing Group
• Subjects: 631/208/212/748; 631/208/457; 631/208/726/649; Alleles; Biomedical and Life Sciences; Biomedicine; Black or African American - genetics; Black People - genetics; Female; Gene Expression; Gene Frequency; Gene Function; Gene Therapy; Genetic diversity; Genome, Human - genetics; Genomes; Human Genetics; Humans; Infant; Lactase; Linkage disequilibrium; Malawi; Male; Molecular Medicine; original-article; Polymorphism, Single Nucleotide; Population - genetics; Single-nucleotide polymorphism; Malawi; Kenya; African ancestry; population genetics; HapMap; population substructure; genome variation; lactase
• ISSN: 1434-5161; 1435-232X; 1435-232X
• DOI: 10.1038/jhg.2010.41

Understanding genetic variation between populations is important because it affects the portability of human genome-wide analytical methods. We compared genetic variation and substructure between Malawians and other African and non-African HapMap populations. Allele frequencies and adjacent linkage disequilibrium (LD) were measured for 617 715 single nucleotide polymorphisms (SNPs) across subject genomes. Allele frequencies in the Malawian population ( N =226) were highly correlated with allele frequencies in HapMap populations of African ancestry (AFA, N =376), namely Yoruban in Ibadan, Nigeria (Spearman's r 2 =0.97), Luhya in Webuye, Kenya ( r 2 =0.97), African Americans in the southwest United States ( r 2 =0.94) and Maasai in Kinyawa, Kenya ( r 2 =0.91). This correlation was much lower between Malawians and other ancestry populations ( r 2 <0.52). LD correlations between Malawians and HapMap populations were strongest for the populations of AFA (AFA r 2 >0.82, other ancestries r 2 <0.57). Principal components analyses revealed little population substructure within our Malawi sample but provided clear distinction between Malawians, AFA populations and two European populations. Five SNPs within the lactase gene ( LCT ) had substantially different allele frequencies between the Malawi population and Maasai in Kenyawa, Kenya (rs3769013, rs730005, rs3769012, rs2304370; P -values <1 × 10 −33 ).