Researchers Scanned 249,796 People for Obesity Genes. What They Found Explains About 1.5% of It
The landmark BMI genome-wide association study confirmed 14 known loci and found 18 new ones, several near hypothalamic regulators of appetite. Together they account for a small fraction of why people differ in weight — which is the most useful thing about them.
Two brothers eat the same dinners, in the same house, for eighteen years. One stays thin. Twin and family studies have been pointing at that puzzle for decades, putting the heritability of body mass index somewhere between 40% and 70%.
So when researchers examined roughly 2.8 million markers against BMI in 123,865 individuals, with follow-up of 42 markers in a further 125,931, the expectation was that the responsible genes would show themselves.
They did. Sort of.
What was found
The study confirmed 14 previously known obesity susceptibility loci and identified 18 new ones — 32 in total (Speliotes et al., Nature Genetics, 2010, PMID: 20935630).
The biology was coherent. Several loci sat near MC4R, POMC, SH2B1 and BDNF — key hypothalamic regulators of energy balance, the circuitry that governs appetite and satiety. Another was near GIPR, an incretin receptor, the same signalling family later targeted by GLP-1 drugs.
The strongest single signal remains FTO, where carrying two copies of the risk allele is associated with an average difference of roughly three kilograms.
The gap nobody could close
Together, those 32 loci explained only around 1.5% of the variation in BMI.
Heritability said 40–70%. The measured variants delivered a couple of percent. This gap — christened the "missing heritability" problem — dominated the field for years.
The resolution turned out to be undramatic. BMI is influenced by an enormous number of variants, each with an effect too small to reach significance in a study of a quarter of a million people. Later studies with far larger samples pushed the count into the hundreds of loci and the explained variance up, but the shape held: thousands of tiny contributions, no master switch.
What this means for you specifically
Three things follow, and they are not the ones usually implied.
Heritability is not personal. A heritability of 60% describes how much of the variation across a population tracks genetic variation in that population. It does not mean 60% of your body weight is genetic.
Small effect sizes cut both ways. FTO is the most famous obesity variant in existence and it corresponds to a few kilograms on average. That is real, and it is not destiny.
Environment is not the leftover. The food environment shifted dramatically over decades in which the gene pool did not. Population-level weight change over the twentieth century is not a genetic story.
None of this is a reason to disregard genetics. It is a reason to read a genetic weight result as one modest input among many.
What the app reports
My Weight applies the loci from the Speliotes analysis to your genotype and shows where you sit on the distribution described in that study.
What it can tell you is whether your genome carries more or fewer of the common variants associated with higher BMI in large European-ancestry cohorts. What it cannot tell you is what you weigh, why, or what to do about it. For that, the useful conversation is with a doctor or dietitian.