Article
Extended Data Fig. 3 | Conditional association analyses for genetic markers
across the extended MHC genomic region within the European-ancestry
SLE and Sjögren’s syndrome cohorts. a, Association of SLE with genetic
markers (SNPs and imputed HLA alleles) across the extended MHC locus within
the European-ancestry SLE cohort (6,748 cases and 11, 516 controls). Orange
diamond: an initial estimate of C4-related genetic risk, calculated as a weighted
sum of the number of C4A and C4B gene copies: (2.3)C4A+C4B, with the weights
derived from the relative coefficients estimated from logistic regression of SLE
risk versus C4A and C4B gene dosages. This risk score is imputed with an
accuracy (r^2 ) of 0.77. Points representing all other genetic variants in the MHC
locus are shaded orange according to their level of LD-based correlation to this
C4-derived risk score. b, As in a, but for a European-ancestry Sjögren’s
syndrome (SjS) cohort (673 cases and 1,153 controls). The orange diamond here
also represents (2.3)C4A + C4B, with this weighting derived from the relative
coefficients estimated from logistic regression of Sjögren’s syndrome risk
versus C4A and C4B gene dosages. c, Association of SLE with genetic markers
(SNPs and imputed HLA alleles) across the extended MHC locus within the
European-ancestry SLE cohort controlling for C4 composite risk (weighted
sum of risk associated with various combinations of C4A and C4B). Variants are
shaded in purple by their LD with rs2105898, an independent association
identified from trans-ancestral analyses. d, As in c, but in association with a
European-ancestry Sjögren’s syndrome cohort. Here a simpler linear model of
risk contributed by C4A and C4B was used instead of a weighted sum across all
possible combinations.