For case-control samples, the ancestry proportion of each subject was estimated using the genotype data of 38 AIMs through application of the program STRUCTURE (35,36). Pair-wise marker LD analyses were performed using the program Haploview 4.0 (29) in cases and controls separately and combined. HWE analyses, allele and genotype frequency calculation, and individual marker association analysis were performed using the program PowerMarker (37). Estimation of haplotype frequencies and examination of the effect of haplotypes on disease traits were conducted using haplotype trend regression (HTR) implemented in HelixTree software (Golden Helix, Inc., Bozeman, MT, USA). Potential confounding effects of sex and age (not matched in our cases and controls) on individual marker or haplotype association results were analyzed using a backward stepwise logistic regression (LR) analysis implemented in SPSS 15.0 (SPSS Inc, Chicago, IL, USA), as described previously (28). The influence of POMC variants on the three disease traits (AD, CD, or OD) was investigated under three models (additive, dominant, and recessive). The disease trait was the dependent variable, and sex, age, and the probabilities of alleles, genotypes, or haplotypes were
