Fig. 1

a Schematic illustration showing alleles of the sentinel SNP rs72959041 and the tagging SNP rs577721086. b Allelic expression analysis of RSPO3 transcripts was performed by qRT-PCR in abdominal and gluteal AT cDNA from 14 heterozygous carriers at rs72959041 (seven females, seven males). The proportion of total cDNA and gDNA containing the (WHR-increasing) rs577721086-C allele (r² = 0.98 with rs72959041-A) is quantified on the y-axis. Error bars are median values with 95% confidence intervals. Statistical significance was assessed by two-tailed paired Student’s t-tests versus gDNA. cRSPO3 WHRadjBMI GWAS signals co-localise with subcutaneous adipose cis-eQTLs. d, e Allelic expression of RSPO3 transcripts were analysed in abdominal and gluteal isolated adipocyte (ADS) (d) and cultured AP (e) cDNAs from ten heterozygous female carriers at rs72959041 as in b. f Schematic illustration showing alleles of the enhancer SNP rs9491696 and the tagging SNP rs1892172. g–i Allelic expression analysis of RSPO3 in g abdominal and gluteal AT cDNA from 32 individuals (15 females, 17 males) and in h abdominal and gluteal ADS and i cultured AP cDNA from 17 and 19 females, respectively, who are heterozygous at rs9491696. All individuals selected are homozygous for the rs72959041-G (non-risk) allele. The proportion of cDNA and gDNA containing the WHRadjBMI-increasing rs1892172-A allele (r² = 0.84 with rs9491696-G) is quantified on the y-axis. Error bars are median values with 95% confidence intervals. Statistical significance was assessed by two-tailed paired Student’s t-tests versus gDNA. j–m Median adipocyte cell weight calculated from median cell area measured from j abdominal and l gluteal AT histological sections from 14 and 15 pairs, respectively, of age- and BMI-matched females grouped by rs72959041 genotype. Cumulative frequency distribution of the adipocyte cell-surface area are shown for abdominal (k) and gluteal (m) AT. More than 250 cells were measured for each biopsy. Box and whisker plot: centre line, median; box limits, upper and lower quartiles; and whiskers, maximum and minimum values. Statistical significance was assessed by a two-tailed Wilcoxon signed-rank test. Source data are provided as a Source Data file.