Fig. 3 | Nature Communications

Fig. 3

From: A reference haplotype panel for genome-wide imputation of short tandem repeats

Fig. 3

STR imputation improves power to detect STR associations. a Example simulated quantitative phenotype based on SSC genotypes. A quantitative phenotype was simulated assuming a causal STR (red). Power to detect the association was compared between the causal STR, imputed STR genotypes, and all common SNPs (MAF > 0.05) within a 50 kb window of the STR (gray). b Strength of association (-log10 p) is linearly related with LD with the causal variant. For SNPs, the x-axis gives the length r2 calculated using observed genotypes. For the imputed STR (blue), the x-axis gives the length r2 from leave-one-out analysis. c The gain in power using imputed genotypes is linearly related to the gain in length r2 compared to the best tag SNP. Gray contours give the bivariate kernel density estimate. Top and right gray area gives the distribution of points along the x- and y-axes, respectively. Power was calculated based on the number of simulations out of 100 with nominal p < 0.05. d Quantile-quantile plot for eSTR association tests. Each dot represents a single STR×gene test. The x-axis gives the expected log10 p-value distribution under a null model of no eSTR associations. Red and blue dots give log10 p-values for association tests using HipSTR genotypes and imputed STR genotypes, respectively. Black dashed line gives the diagonal. e Comparison of eSTR effect sizes using observed vs. imputed genotypes. Each dot represents a single STR×gene test. The x-axis gives effect sizes obtained using imputed genotypes. Gray dots give the effect size in GTEx whole blood using HipSTR genotypes. Purple dots give effect sizes reported previously17 in lymphoblastoid cell lines. f, g Example putative causal eSTRs identified using imputed STR genotypes. Left, middle, and right plots give HipSTR STR dosage (red), imputed STR dosage (blue), and the best tag SNP genotype (gray) vs. normalized gene expression, respectively. STR dosage is defined as the average length difference from hg19. One dot represents one sample. P-values are obtained using linear regression of genotype vs. gene expression. STR and SNP sequence information is shown for the coding strand. Gene diagrams are not drawn to scale

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