Hormonal
Integrating multiple computational gene prioritization methods (SMR, FINEMAP, DEPICT, MAGMA, TWAS, MSC, PoPS, nearest gene) identifies 292 high-confidence candidate genes associated with BMI, many of which regulate neuronal body weight control, circadian rhythm, insulin secretion, and glucose homeostasis.
This research does not offer a direct lifestyle intervention but highlights that obesity has strong genetic underpinnings involving brain regulation, insulin, and circadian rhythms. Understanding these specific biological pathways can help explain why weight loss is difficult for some and points toward future targeted therapies (e.g., drugs affecting GIPR or FGFR1) rather than just willpower-based approaches.
We identified 292 high-scoring genes (R11) in 264 loci... Many of the top-scoring genes seem to act through a neuronal regulation of body weight, whereas others affect peripheral pathways, including circadian rhythm, insulin secretion, and glucose and carbohydrate homeostasis.
Why this rating
High-quality computational genetics using large GWAS datasets (N > 700,000) and multiple orthogonal validation methods.
Source
An integrative framework to prioritize genes in more than 500 loci associated with body mass index
Daiane Hemerich et al. · The American Journal of Human Genetics · 2024
DOI 10.1016/j.ajhg.2024.04.016
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