The familial relative risk to a first degree relative accounted for by an individual variant (denoted as λi) is estimated based on relative risk per allele and allele frequency for that variant, using the method described in Hemminki et al41, and Bahcall42, under the assumption of log-additive effect. Assuming the effects of all susceptibility variants combined multiplicatively and not in linkage disequilibrium, the combined effect (λT) can then be expressed as the product of all λi. The proportion of the familial relative risk attributable to the totality of the susceptibility variants can then be computed as log(λT)/log(λP). For lung cancer, the λP is approximately 2.0 based on the family cancer databases26,27. The percentage reported is based on the 18 sentinel variants reported in Table 2. The multiple independent alleles in the same locus are not accounted for in this estimation.
