title: Comparison of genome-wide variation between Malawians and African ancestry HapMap populations.
abstract: 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 x 10(-33)).
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA. joubert.bonnie@epa.gov
authors.forename: Bonnie R
authors.initials: BR
authors.lastname: Joubert
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wang
authors.forename: Victor
authors.initials: V
authors.lastname: Mwapasa
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
mesh_terms: D001741:Black or African American / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D007223:Infant; D008295:Malawi; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011153:Population / Q000235:genetics