This article is from The Scientist this past week.
First is the lay summary. Below is the scientific summary from the Cell Rep publication. One question that immediately formed in my mind is that “body shape” is different for various ethnic groups. In the title of the paper, the authors include “body shape” as associated with this allele –– but their cohort of more than 451,000 people was only Europeans (well, at least from the UK Biobank). Unfortunately, there are no statistics included in the Abstract. If one cares to study this further, the statistics are summarized below and shown in Table 1 of the Cell Rep publication.
A study of more than 450,000 people finds a certain genetic variant associated with eating more carbs is linked to a thicker waist and higher blood pressure, but less fat.
By Kerry Grens
April 11, 2018
A variant in the gene for a certain hormone is tied to people who tend to eat more carbs. Yet a new study of 451,000 people finds that this allele doesn’t universally mean obesity or poorer health. Researchers reported yesterday (April 10) in Cell Reports that those with the sweet-tooth allelic variant actually have lower body fat than others, and no higher risk for type-2 diabetes. They did, however, find a link between the allele and high blood pressure and a thicker waistline.
“This goes against the current perception that eating sugar is bad for health. It may reduce body fat because the same allele also results in a lower consumption of protein and fat in the diet,” study coauthor Timothy Frayling, a molecular geneticist at the University of Exeter Medical School in the U.K., says in a press release. “But whilst this version of the gene lowers body fat, it also redistributes fat to the upper body, where it’s more likely to cause harm, including higher blood pressure.”
The gene of interest here is FGF21, which encodes fibroblast growth factor-21, a hormone involved in alcohol and sugar consumption and insulin sensitization. The authors note that it’s already a target of weight loss interventions.
People with a particular allele of FGF21 — 20 percent of Europeans are homozygous for the variant — tend to consume relatively more sweets and alcohol than those without the allele. To see what consequences this might have on people’s health, Frayling and his colleagues collected data on 451,000 people whose genetic and health information is part of the UK Biobank.
Although those with the sweet-tooth allele had less body fat than others, they had a higher waist-to-hip ratio. They also had higher blood pressure, but no greater risk for heart disease or type 2 diabetes. “These results suggest that FGF21 has pleiotropic effects, with separate effects on macronutrient intake to those on body shape and blood pressure,” the authors write in their report.
Stephen Simpson, a nutrition scientist at Sydney University, tells Cosmos that the results may warrant a rethink of the idea that “no matter what, sugar consumption is bad. This villainization needs proper exploration.”
Tags: weight, sweet, insulin, hormones, heart disease , genetics & genomics, fat, epidemiology, diet, diabetes,carbs and body fat
Below is the scientific summary from the Cell Rep publication:
Summary (from the article in Cell Reports)
Fibroblast growth factor 21 (FGF21) is a hormone that has insulin-sensitizing properties. Some trials of FGF21 analogs show weight loss and lipid-lowering effects. Recent studies have shown that a common allele in the FGF21 gene alters the balance of macronutrients consumed, but there was little evidence of an effect on metabolic traits. We studied a common FGF21 allele (A:rs838133) in 451,099 people from the UK Biobank study, aiming to use the human allele to inform potential adverse and beneficial effects of targeting FGF21. We replicated the association between the A allele and higher percentage carbohydrate intake. We then showed that this allele is more strongly associated with higher blood pressure and waist-hip ratio, despite an association with lower total body-fat percentage, than it is with BMI or type 2 diabetes. These human phenotypes of variation in the FGF21 gene will inform research into FGF21’s mechanisms and therapeutic potential.
We used a p value of 0.0005 as an equivalent of p = 0.05 given the 100 tests performed. In Table 1 we show how each copy of the minor A allele was associated with higher self-reported estimates of carbohydrate and alcohol intake and lower fat and lower protein intake. All these associations reached genome-wide levels of statistical confidence. These effects imply very strongly that the rs838133 A allele (population frequency = 45%) results in lower FGF21 function because genetic and pharmacological lowering of FGF21 in animal models, including non-human primates, has exactly the same effect on carbohydrate and alcohol preferences (Talukdar et al., 2016a, von Holstein-Rathlou et al., 2016).