Genotyping of the discovery dataset was generated by either whole genome sequencing (WGS) and/or genome-wide genotyping by either Illumina OmniQuad Express or Affymetrix GeneChip 6.0 platforms, as described52,53. We prioritized using WGS over genotyping where available and performed quality control of WGS and genotyping data separately using Plink54. We excluded individuals with genotyping missing rate >5%, variants with Hardy Weinberg equilibrium p-value < 1E-08, variants with missing genotype rate >5%, variants with minor allele frequency <1%, and variants that are not single nucleotide polymorphisms (SNPs). We used KING to remove individuals who were estimated to be closer than second degree kinship55. Genotyping for each individual was imputed to the 1000 Genome Project Phase 356 using the Michigan Imputation Server57 and SNPs with imputation R2 > 0.3 were retained. Finally, genotyping was filtered to include 1,190,321 HapMap SNPs from the 489 individuals of European descent from the 1000 Genomes Project16, which is provided by FUSION and often referred to as the linkage disequilibrium (LD) reference panel. After quality control, 376 subjects with both proteomic and genetic data were included in the discovery analyses. Of these, 262 subjects were female and mean age at death was 89 years old.
