# Association tests

## Endpoint

We included ​​**3,095**​ endpoints in the analysis. Endpoints with less than 80 cases or less than 1,000 controls among the **309,154** samples were excluded, as well as endpoints labeled with an OMIT tag in the endpoint definition file.

## Null models

For regenie step 1 LOCO prediction computation for each endpoint, we used age, sex, 10 PCs, Finngen 1 or 2 chip or legacy genotyping batch as covariates.

The null model didn’t initially converge for three phenotypes: L12\_ALOPECANDRO, DRY\_AMD and N14\_ENDOMETRIOSIS\_FALLOPIAN\_TUBE. For the first two, we excluded legacy batches with less than 10 cases from covariates and for N14\_ENDOMETRIOSIS\_FALLOPIAN\_TUBE, we excluded all legacy batches from covariates, and the nulls converged successfully.

For calculating genetic relatedness in regenie step 1, we included variants 1) imputed with an INFO score > 0.95 in all batches and 2) > 97 % non-missing genotypes and 3) MAF > 1 %. The remaining variants were LD pruned with a 1Mb window and r2 threshold of 0.1. This resulted in a set of 55,139 well-imputed not rare variants for relatedness calculation.

We used a genotype block size of 1,000 in regenie step 1.

## Association tests

We ran association tests with regenie for each of the 3,095 endpoints for each variant with a minimum allele count of 5 among each phenotype’s cases and controls. We used the approximate Firth test for variants with an initial p-value of less than 0.01 and computed the standard error based on effect size and likelihood ratio test p-value (regenie options --firth --approx --pThresh 0.01 --firth-se).


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