Panel A: association of the 53-SNP genetic score with
anthropometric and glycaemic traits in meta-analyses of genetic association
studies. Body mass index (BMI), waist-to-hip ratio (WHR), waist and hip
circumference data are from the GIANT consortium and the UK Biobank study. Body
fat percentage data are from the UK Biobank, EPIC-Norfolk and Fenland studies.
Fasting plasma glucose (FPG), 2 hour glucose and HbA1c data are from the MAGIC
consortium. Squares with error bars represent the per-allele beta coefficients
in standard deviation units and their 95% confidence intervals. Panel
B: association of genetic scores with compartmental body masses.
Data are from 12,848 participants of the Fenland and EPIC-Norfolk studies who
underwent a DEXA scan. Squares with error bars represent the per-allele beta
coefficients in standard deviation units and their 95% confidence intervals.
Panel C: association with lower levels of leg fat mass and
higher hazard of incident type 2 diabetes by quintiles of the 53-SNP genetic
risk scores. Associations are reported for individuals in the exposed category
compared with the bottom quintile (reference category). Associations with leg
fat mass are from 9,747 participants of the Fenland study and are reported on
the left. Associations with incident type 2 diabetes are from 7,420 incident
cases and 9,267 controls of the InterAct study and are reported on the right.
Squares represent the beta coefficients in grams of leg fat mass (left plot) or
the hazard ratio (HR) for incident type 2 diabetes (right plot) in each category
compared with the lowest quintile. Error bars represent the 95% confidence
intervals of these estimates. Panel D: associations of
individual lead SNPs at eight loci with waist, hip circumference (left) and type
2 diabetes (right). Loci were selected on the basis of their genome-wide
significant association with hip circumference or body fat percentage (i.e.
PIK3R1). Waist and hip circumference analyses are from a
meta-analysis of the GIANT and UK Biobank studies. Type 2 diabetes analyses are
from a meta-analysis of the DIAGRAM, InterAct and UK Biobank studies. Squares
with error bars represent the per-allele beta coefficients in standard deviation
units of waist and hip circumference (left plot) or the per-allele odds ratio
(OR) of type 2 diabetes (right plot). Error bars represent the 95% confidence
intervals of these estimates. *Detailed associations at the
PIK3R1 locus, which was primarily associated with lower
body fat percentage, are presented in Supplementary Figure 9.