For the analyses, we first subdivided subjects into ancestral groups based on identity-by-state sharing, as estimated using the genotyped SNPs in parents or, if they had not undergone genotyping, 1 randomly selected sibling per family. Three well-distinguished clusters, where the major self-reported ethnicity in each group was African (1262 individuals from 438 families), European (2740 individuals from 794 families), and Asian (2296 individuals from 579 families) ancestry, are shown in eFigure 7. Next, we used UNPHASED software,16 which is robust to population structure when the data are complete and has only minor loss of robustness when data are missing. To further minimize the risk of population stratification effects, we first performed the analyses within each ancestral group and then combined the 3 test statistics to obtain an overall replication P value. We limited the association testing to markers with a minor allele frequency of greater than 0.05 within each group. We preserved the direction of effects (ie, sign) so that an allele being overtransmitted in one group and undertransmitted in another would have no effect in this combined analysis (eMethods 2). Additional details are given in eTable 2 and eFigure 8.
