Examining the genes at BMI-associated loci in the context of gene expression, molecular pathways, eQTL results, mutational evidence and genomic location provides several complementary avenues through which to prioritize genes for relevance in BMI biology. Genes such as NPC1 and ELAVL4 are implicated by many lines of evidence (literature, mutational, eQTL and DEPICT) and become strong candidate genes in their respective locations. It is important to recognize that pathway methods and literature reviews are limited by current data sets and knowledge, and thus provide only a working model of obesity biology. For example, little is known about host genetic factors that regulate the microbiome. Variation in immune-related genes such as TLR4 could presumably exert an influence on obesity through the microbiome35. Together, our results underscore the heterogeneous aetiology of obesity and its links with several related metabolic diseases and processes.
