Extended Data Fig. 2 | Aggregation of joint C4A and C4B genotype
probabilities per individual across imputed C4 structural alleles for
estimation of SLE risk for each combination. a, An individual’s joint C4A and
C4B gene copy number can be calculated by summing the C4A and C4B gene
contents for each possible pair of two inherited alleles. Many pairings of
possible inherited alleles result in the same joint C4A and C4B gene copy
number. b, Each individual’s C4A and C4B gene copy number was imputed from
their SNP data, using the reference haplotypes summarized in Extended Data
Fig. 1c. For more than 95% of individuals (exemplified by samples 1–6 in the
figure), this inference can be made with >90% certainty or confidence (the
areas of the circles represent the posterior probability distribution over
possible C4A/C4B gene copy numbers). For the remaining individuals
(exemplified by samples 7–9 in the figure), greater statistical uncertainty
persists about C4 genotype. To account for this uncertainty, in downstream
association analysis, all C4 genotype assignments are handled as probabilistic
gene dosages—analogous to the genotype dosages that are routinely used in
large-scale genetic association studies that use imputation. c, Odds ratios and
95% confidence intervals underlying each of the C4-genotype risk estimates in
Fig. 1a presented as a series of panels for each observed copy number of C4B,
with increasing copy number of C4A for that C4B dosage (x-axis). Data are from
analysis of 6,748 SLE cases and 11, 516 controls of European ancestry.