coded genotypes “0” for common allele homozygotes,11 “1” for heterozygotes, and “2” for rare allele homozygotes,22 and for ADAMTS9, BCL11A, CALPN10, CDKN2A/2B, HHEX, JAZF1, PPARG, SLC30A8, and THADA, coding was “2” for common allele homozygotes and “0” for rare allele homozygotes,11 as the rare allele is reported to be protective (see web table B). In the second score, we calculated a genetic risk function by using weights derived from the risk coefficient for each gene based on odds ratios reported in previous meta-analyses (web table A).15 16 18 32 Risk estimates for each allele were available for 18 genes, and we multiplied these coefficients by 0, 1, or 2 according to the number of risk alleles carried by each person. Where effect estimates were reported for carriage of either one or two copies of each risk allele as a single group (CALPN10 and HNF1A), we multiplied risk coefficients by a score of 0 or 1. We assumed genetic and clinical variables to be independent and added the weighted genetic score to each of the risk algorithms to provide a combined phenotypic and genetic score.
