The top genes with the highest CrF for P + LP variants were G6PD (XL, favism) for Africans (1/5 individuals; 255 million individuals); GJB2 (AD, palmoplantar keratoderma) for East Asians (1/10; 198 million); and HFE (AR, hemochromatosis) for non-Finnish Europeans (1/3; 335 million), Finnish (1/4; 1.37 million), Ashkenazi Jews (1/4; 3.51 million), Middle Easterners (1/5; 111 million), Admixed Americans (1/5; 151 million) and South Asians (1/7; 293 million), which was driven by two missense variants with penetrance as low as 4.5% [30] (Fig. 2A and Additional File 1: Tables S3 and S6). Here, G6PD is linked to hereditary palmoplantar keratoderma.