The score test is known to slightly underestimate additive effect sizes 34, so the top association per probe was validated with a linear mixed-effects model in R, using the lmer() function in the lme4 package 39, fitted by maximum-likelihood(Supplementary Fig. 2). The linear mixed-effects model were adjusted for both fixed (age, experimental batch effect and sample processing effect (skin tissue only)) and random effects (family relationship and zygosity). A likelihood ratio test was applied to assess the significance of the SNP effect. The p-value of the SNP effect in each model was calculated from the Chi-square distribution with 1 degree of freedom using -2log(likelihood ratio) as the test statistic.
