Additional file 1 of M3-S: a genotype calling method incorporating information from samples with known genotypes

Supplemental Materials. A: Concordance among replicates of HapMap samples. B: Computational time of M3-S. C: Comparison of different measures in reference SNP selection, D: Comparison of different calling methods. E: The effect of the threshold. (PDF 89 kb

Estimated PIPs by SuSiE, SuSiE² and eQTL-based SuSiE for PICALM (A) and C14orf93 (B).

The PIPs estimated from the eQTL study are used as the prior information by SuSiE for SuSiE2. For the PICALM locus, PIPs for the true mediator in this locus are surrounded by the purple circle, and the points surrounded by an orange triangle correspond to the credible set from SuSiE2 which can capture the true mediator. For the C14orf93 locus, the true mediator was not included in the common part of summary statistics and ROSMAP data.</p

Estimated PIP for each AD mediator by SuSiE and SuSiE².

There were in total 20 AD risk loci divided into the following three categories. Five mediators were captured by both SuSiE and SuSiE2 in one credible set, denoted by the blue dots. SuSiE2 identified four additional risk loci, denoted by the green dots. The remaining 11 loci could not be captured in any credible set by either SuSiE or SuSiE2, corresponding to the red dots.</p

Average size of credible sets by SuSiE and SuSiE².

We applied the SuSiE2 pipeline with gene expression from subcutaneous adipose (left) and visceral adipose (right). The 95% credible sets were grouped according to the chromosome in which they are located, labeled by chri for the ith chromosome. The minimum absolute correlation allowed in a credible set was fixed at 0.9 for both SuSiE and SuSiE2.</p

Summary of credible sets detected by SuSiE and SuSiE² in the BMI study.

Summary of credible sets detected by SuSiE and SuSiE2 in the BMI study.</p

Comparison of SuSiE² when using in-sample or external LD matrices for the first step of SuSiE².

We compare the 95% credible sets from SuSiE2 when using either the in-sample LD matrix () or the LD matrix from 1KG panel () in the eQTL-based SuSiE. For each combination of method and heritability, we show the mean value and the standard error from 150 repetitions. Panel A evaluates the power of detecting causal SNPs in at least one credible set. Panel B evaluates the coverage of credible sets, with the black dashed line corresponding to the 95% level. For the second step of SuSiE2 (fine-mapping for the trait of interest), we always used the LD matrix from the 1KG reference panel. (TIF)</p

Comparison of methods in simulated data with the in-sample LD matrix.

We assess the 95% credible sets generated by five fine-mapping methods (SuSiE, SuSiE2, mvSuSiE, flashfm, fastPAINTOR) under two scenarios (a) (A, B, C) and (b) (D, E, F). The results, averaged over 100 repetitions for each method and heritability combination, are presented with both the mean value and the empirical standard error. Panels A and D evaluate the power of detecting causal SNPs in at least one credible set. Panels B and E focus on the coverage of credible sets, with the black dashed line indicating the 95% level. Panels C and F evaluate the average size of credible sets for scenarios (a) and (b), respectively.</p

Fine-mapping examples on BMI risk loci with SuSiE and SuSiE².

The plots show the estimated PIPs for each SNP in two risk regions by SuSiE and SuSiE2. Panel A presents the results for a risk region on chromosome 1. Panel B illustrates the results for a risk region on chromosome 6. The SNPs from the same 95% credible sets by SuSiE or SuSiE2 are surrounded by circles in the same corresponding color. We label each credible set with the SNP ID of the leading variant.</p

Comparison of methods in simulated data with the 1KG reference panel.

We compare the 95% credible sets from five fine-mapping methods (SuSiE, SuSiE2, mvSuSiE, flashfm, fastPAINTOR) under scenarios (b). For each combination of method and heritability, we present the mean value and the standard error from 100 repetitions. Panel A gives summaries of the power of detecting causal SNPs in at least one credible set. Panel B evaluates the coverage of credible sets, with the black dashed line corresponding to the 95% level. Panel C evaluates the average size of credible sets.</p

Summary of credible sets identified by SuSiE and SuSiE².

Summary of credible sets identified by SuSiE and SuSiE2.</p