Extended Data Figure 4: Heat map of unsupervised hierarchical clustering of the effects of 49 WHRadjBMI SNPs on 22 anthropometric and metabolic traits and diseases.

The matrix of Z-scores representing the set of associations was scaled by row (locus name) and by column (trait) to range from −3 to 3. Negative values (blue) indicate that the WHRadjBMI-increasing allele was associated with decreased values of the trait and positive values (red) indicate that this allele was associated with increased values of the trait. Sample sizes for the associations are listed in Supplementary Table 8. Dendrograms indicating the clustering relationships are shown to the left and above the heat map. The WHRadjBMI-increasing alleles at the 49 lead SNPs segregate into three major clusters comprised of alleles that associate with: (1) larger WCadjBMI and smaller HIPadjBMI (n = 30 SNPs); (2) taller stature and larger WCadjBMI (n = 8 SNPs); and (3) shorter stature and smaller HIPadjBMI (n = 11 SNPs). The three visually identified SNP clusters could be statistically distinguished with >90% confidence. Alleles of the first cluster were predominantly associated with lower high density lipoprotein (HDL) cholesterol and with higher triglycerides and fasting insulin adjusted for BMI (FIadjBMI). BMD, bone mineral density; eGFRcrea, estimated glomerular filtration rate based on creatinine; LDL cholesterol, low-density lipoprotein cholesterol; UACR, urine albumin-to-creatinine ratio.