A gene previously suspected of wielding the single greatest genetic influence on human obesity actually has nothing to do with body weight, according to a new study led by researchers at Harvard Medical School and Boston Children’s Hospital.
The work not only overturns a major finding about the genetics of obesity but also provides the first effective ways to analyze “particularly ornery and confusing” parts of the genome, such as the locus of this gene, said the study’s co-senior author, Steven McCarroll, assistant professor of genetics at HMS.
He analyzed genome-wide association data collected by the GIANT Consortium and found no association between AMY1 and body mass index, a measure of a person’s weight relative to their height. But because that region of the genome was so complicated, with AMY1 varying so widely (from two to 14 or more copies per person), he wasn’t sure his data told the whole story.
“There are hundreds of loci in the human genome with this kind of complexity. They have been like black holes in our knowledge of the human genome,” said McCarroll. “I think this is the beginning of a playbook for making sense of those regions.”
“If AMY1 had been a simple variant, it would have been really surprising to see opposite results like this,” said Hirschhorn. “We’ve established best practices for identifying and confirming simple variants, but complex variants are not at that stage yet. This is a younger field having its birth pangs.” More.
Of course, before we heard that, we had heard, in “Starchy Dangers in Human Evolution”:
Furthermore, variation in AMY1 copies may account for somewhere between 2.5% and 20% of all variation in risk of besity among people. Prior to this study, all of the hundreds of genetic variants found to be associated with obesity accounted together for only 2-4% of the genetic risk of obesity, or less than 3% of the overall risk of obesity.
Note that little damage is done to the overall credibility of human evolution claims that so many are shown to be incorrect. However inevitable, that outcome should detract from their credibility, not provide an excuse for lack thereof. But it doesn’t, because they are not really science claims in the first place.
See also: There’s a gene for that… or is there?:
… in the real world of careful analysis, scientists are just not finding the “genes” that the headline writers need. British geneticist Steve Jones points out that most human traits are influenced by so many genes that there is no likely systematic cause and effect:
We know of more than 50 different genes associated with height … That has not percolated into the public mind, as the Google search for “scientists find the gene for” shows. The three letter word for — the gene FOR something — is the most dangerous word in genetics.
And the craze is not harmless, he warns. …
Here’s the abstract:
Hundreds of genes reside in structurally complex, poorly understood regions of the human genome1, 2, 3. One such region contains the three amylase genes (AMY2B, AMY2A and AMY1) responsible for digesting starch into sugar. Copy number of AMY1 is reported to be the largest genomic influence on obesity4, although genome-wide association studies for obesity have found this locus unremarkable. Using whole-genome sequence analysis3, 5, droplet digital PCR6 and genome mapping7, we identified eight common structural haplotypes of the amylase locus that suggest its mutational history. We found that the AMY1 copy number in an individual’s genome is generally even (rather than odd) and partially correlates with nearby SNPs, which do not associate with body mass index (BMI). We measured amylase gene copy number in 1,000 obese or lean Estonians and in 2 other cohorts totaling ~3,500 individuals. We had 99% power to detect the lower bound of the reported effects on BMI4, yet found no association. (paywall) – Christina L Usher, Robert E Handsaker, Tõnu Esko, Marcus A Tuke, Michael N Weedon, Alex R Hastie, Han Cao, Jennifer E Moon, Seva Kashin, Christian Fuchsberger, Andres Metspalu, Carlos N Pato, Michele T Pato, Mark I McCarthy, Michael Boehnke, David M Altshuler, Timothy M Frayling, Joel N Hirschhorn, Steven A McCarroll. Structural forms of the human amylase locus and their relationships to SNPs, haplotypes and obesity. Nature Genetics, 2015; DOI: 10.1038/ng.3340
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