Fig. 4: Coding variants within segmental duplications underlie top genetic associations with T2D and chronotype.

a,b, Genome-wide associations with T2D (a) and chronotype (b). c, Associations of variation at 7q22.1 with chronotype and T2D. Associations of PSVs within the 99-kb repeat at this locus (1–7 copies per allele; two copies in GRCh37) are plotted in the center; the green dashed line indicates the association strength of copy number of the 99-kb repeat. d, Joint distribution of copy number estimates for the 99-kb segmental duplication and the RASA4 Y731C missense variant. e, T2D prevalence and mean chronotype (in standardized units; higher for ‘evening people’) as a function of the number of copies of the RASA4 Y731C missense variant. f, T2D associations at the CTRB2 locus; the colored dots are variants in partial LD (r² > 0.01) with the CTRB2 exon 6 deletion. g, Location of the 584-bp deletion spanning CTRB2 exon 6 (top) and exome sequencing read alignments for a deletion carrier (bottom); most reads aligned to the region paralogous to CTRB1 do not map uniquely and are colored white. h, Scatter plot of normalized whole-genome and WES read depths at CTRB2 exon 6. i, Mean HbA1c and prevalence of T2D and pancreatic cancer as a function of CTRB2 exon 6 deletion genotype. The error bars represent the 95% CIs. The sample sizes for HbA1c are reported in Supplementary Data 1; n = 453,585 for T2D; n = 454,633 for pancreatic cancer; n = 406,359 for chronotype.