Association tests

Null models

For the null model calculation for each endpoint, we used age, sex, 10 PCs and genotyping batch as covariates.

For calculating the genetic relationship matrix, we used 49,811 independent, common, well-imputed variants with a posterior genotyping probability >0.95 and missingness <0.05 (LD r2 < 0.1, MAF > 0.05, INFO > 0.95).

SAIGE options for the null computation:

• LOCO = false

• numMarkers = 30

• traceCVcutoff = 0.0025

• ratioCVcutoff = 0.001

Association tests

We ran association tests against each of the 1,122 endpoints with for each variant with a minimum allele count of 10 from the imputation pipeline (SAIGE optionminMAC = 10). The alternative allele is always the effect allele.

Software

The code we used is available in . The original SAIGE codebase is available in .