Abstract
Body mass and composition are complex traits of clinical interest due to their links to cardiovascular- and metabolic diseases. In this study, we performed genome-wide association studies (GWAS) for the distribution of body fat to the arms, legs and trunk. Proportions of fat, distributed to the different compartments, were calculated for 362,499 individuals from the UK biobank, based on segmental bioimpedance analysis (sBIA) estimates. A total of 85 body fat distribution loci were identified, using data from 116,138 participants, and replicated in an independent set of participants (N = 246,361). Out of these loci, 28 were associated with the proportion of fat in the arms, 43 with the legs and 57 with the trunk. A large degree of overlap was observed between legs and trunk loci (N=33), while arm loci overlapped to a smaller degree with leg and trunk loci (N=4 and 6, respectively). As many as 50 of the loci have not previously been associated with any adiposity-related trait. Within the novel loci we found lipid metabolism-related genes such as CILP2 and OSBPL7, as well as androgen receptor function-related genes such as ESR1, ID4 and ADAMTS17. Significant interactions between the top SNP and sex were observed for 38 loci. Our findings provide evidence for multiple loci that affect the distribution of body fat to discrete compartments of the human body, and highlight that genetic effects differ between men and women, in particular for distribution of body fat to the legs and trunk.