Fig. 10: Pancreatic islet δ cell composition is associated with a genetic risk score for type 2 diabetes derived from genome-wide association studies.
From: Heterogeneous endocrine cell composition defines human islet functional phenotypes
a, b Heatmaps depicting coefficients of the GRS for (a) T1D and (b) T2D, along with partitioned GRS variables after being incorporated into multivariable regression models for each islet composition variable (n = 268). Each model included the following covariates: donor age, sex, BMI, islet isolation center, pre-shipment culture time, islet transit time, and the first five principal components explaining primary genetic ancestry, with the HbA1c covariate (top) or without HbA1c covariate (bottom). “T1D GRS” encompasses the genetic risk for T1D (67 total variants). “HLA DR/DQ” represents the sum of T1D risk at HLA-DR/DQ haplotypes. “HLA Class 1” and “HLA Class 2” represent the sum of T1D risk at HLA class 1 and 2 alleles, respectively, excluding HLA DR/DQ haplotypes. “Non-HLA” represents the sum of T1D risk from variants outside the HLA region, genome-wide. “T2D GRS” encompasses genetic risk for T2D (338 total variants). “Beta Cell,” “Proinsulin,” “Obesity,” “Lipodystrophy,” and “Liver/Lipid” represent partitioned T2D GRS clusters encoding the related variants. Shading represents different regression coefficients. P values are based on the two-sided t-test, and adjusted p values, using the false discovery rate correction, are indicated where *p < 0.05. Comparisons where the unadjusted p-value (punadj) was significant are noted in italics. P values and test statistics are reported in Source Data Fig. 10. c Clustering of the HPAP single-cell RNA-seq data from 44 HPAP donors without diabetes. d The number of cells of each type included in the analysis, including 1877 δ cells. Colors on the heatmap and graph represent different cell types. e The number of genes that were differentially expressed, with three different thresholds for expression, in δ cells. f A dot plot showing T2D GRS genes that are differentially expressed in δ cells (significant genes are shown in blue). Circle size represents the fraction of cells in each group (%) and pink shading represents mean expression in group. g A heat map illustrating T2D GRS genes that are differentially expressed in δ cells (significant genes are shown in blue and shading represents different log2FC). Abbreviations: T1D type 1 diabetes; T2D type 2 diabetes; GRS genetic risk score.
