inbreeding coefficient), f, whose use gives p11=p12+p1(1−p1)f,p12=2p1(1−p1)(1−f),p22=(1−p1)2+p1(1−p1)f, so that f = 0 recovers the HWE model. Examining point and interval estimates for f yields insight into departures from HWE: positive values are manifested in an excess of homozygotes (and may indicate inbreeding) while negative values correspond to an excess of heterozygotes. Defining pmin = min(p1, 1 – p1), the range of f is (−pmin1−pmin,1), and so depends on the allele frequencies, which complicates inference. In a GWAS, f > 0 may indicate population stratification, while f < 0 may occur if there are regions of low-copy repeats, leading to an increase in the number of apparent heterozygotes (Wigginton et al., 2005).
