A maximal set of unrelated individuals was chosen for each analysis using a segmental identity-by-descent (IBD) estimation algorithm33. Individuals were defined as related if they shared more than 700 cM IBD, including regions where the two individuals share either one or both genomic segments identical-by-descent. This level of relatedness (roughly 20% of the genome) corresponds approximately to the minimal expected sharing between first cousins in an outbred population. When constructing the replication cohort, we identified unrelated individuals who were also unrelated to all individuals used in the discovery analysis.
