Genetic instruments selection
Single nucleotide polymorphisms (SNPs) that were genome-wide significant
(P < 5 × 10-8) were extracted from
each GWAS of sex hormones. A stringent linkage disequilibrium (LD)
clumping strategy was then applied, using a window of 10 Mb and
r2 threshold of less than 0.001. We used the 1000
Genomes Project European samples as the LD reference in PLINK 1.9. After
LD clumping, statistically independent SNPs were selected as genetic
instruments for sex hormones.
If genetic instruments were not available in the summary data of
COVID-19 outcomes, we used a proxy variant that was identified in 1000
Genomes Project European samples using LDlink
(https://ldlink.nci.nih.gov/?tab=ldproxy). We harmonized the
SNP-exposure and SNP-outcome summary datasets using a previously
described method 22. During the data harmonization
process, SNPs with a minor allele frequency > 0.49 were
excluded. The number of genetic variants after LD clumping and IVs for
each sex hormone are listed in eTable 1 and eTable 2 .