The SUGEN program19 is a command-line software program developed for genetic association analysis under complex survey sampling and relatedness patterns. It implements the generalized estimating equation method, which does not require modelling of the correlation structures of complex pedigrees. It adopts a modified version of the ‘sandwich’ variance estimator, which is accurate for low-frequency SNPs. Association testing in SUGEN requires the formation of ‘extended’ families by connecting the households who share first-degree relatives or either first- or second-degree relatives. Trait values are assumed to be correlated within families but independent between families. In our experience in analysing this dataset, it is sufficient to account for first-degree relatedness. The current version of SUGEN can accommodate continuous, binary and age-at-onset traits. A comparison of P values produced by SUGEN and GENESIS for all previously identified known loci are included in Supplementary Fig. 12 and Supplementary Table 4.
