Sometimes it’s just as important to rule a gene out as the cause of a condition as it is to rule it in, especially for complex, multi-gene traits like obesity. In a report published yesterday by Nature Genetics, a gene once thought to be the single greatest genetic influence on human obesity actually has nothing to do with body weight.
The study, led by researchers at Harvard Medical School (HMS) and Boston Children’s Hospital, also provides the first effective ways to analyze complicated parts of the genome.
The gene in question, AMY1, encodes an enzyme in our saliva that helps convert starch into sugar. “There’s been some speculation that because this enzyme helps get nutrients out of our food, it could be linked to obesity,” said Christina Usher, a graduate student at HMS and first author on the paper.
What’s complicated is that people can have anywhere from 2 to 14 copies of AMY1—or more. In 2014, an unrelated international group reported in Nature Genetics that people with fewer than four copies of AMY1 had a roughly eight times greater risk for obesity than people with more than nine copies of the gene. AMY1 therefore appeared to be protective.
The HMS–Boston Children’s team, led by Steven McCarroll, PhD, and Joel Hirschhorn, MD, PhD, respectively, ran their own analysis incorporating molecular and mathematical strategies for studying complex variation. AMY1 turned out to have nine common forms, and when the researchers applied their analytic tools to the genomes of about 4,500 Europeans, the AMY1 association with body mass index disappeared.
Learn more in the video below and this press release from HMS.