Hormonal
Rare and low-frequency coding genetic variants in genes such as MC4R, GIPR, and KSR2 are significantly associated with Body Mass Index (BMI), with effect sizes approximately ten times larger than those of common variants.
Your genetics play a role in your weight, but for most people, common lifestyle factors (diet, activity) are far more impactful than rare genetic mutations. If you have a known high-impact mutation like MC4R p.Tyr35Ter, you may need more aggressive or specialized medical interventions, but for the general population, focusing on energy balance remains the most effective strategy.
The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers.
Why this rating
Meta-analysis of 718,734 individuals with array-wide significance thresholds.
Source
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
Valérie Turcot et al. · Nature Genetics · 2017
DOI 10.1038/s41588-017-0011-x
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