Results
We first investigated the association between the FGF21 variant and
macronutrient and alcohol intake. The G (major) allele of rs838133 was
associated with lower intake of total sugars and alcohol, and higher
intakes of protein and fat (Figure 1), consistent with the expected
effect of an increase in FGF21 concentration.2 We
scaled all results per additional G allele to mimic the effect of
elevated FGF21 concentrations.
Higher genetically proxied FGF21 concentration was associated with
greater body mass index, body fat percentage and waist and hip
circumferences, but with lower waist-to-hip ratio (Figure 1).
Additionally, higher genetically proxied FGF21 concentration was
associated with lower concentrations of low-density lipoprotein
cholesterol and triglycerides, lower systolic and diastolic blood
pressure, and lower C-reactive protein concentrations, but was not
associated with fasting glucose or fasting insulin (Figure 1). There was
a positive association of higher genetically proxied FGF21 concentration
with the liver enzyme alkaline phosphatase, but a negative association
with aspartate aminotransferase, gamma glutamyltransferase, and direct
and total bilirubin concentrations (Figure 1). There was suggestive
evidence of a positive association between genetically proxied FGF21
concentration and lifespan (based on parental lifespan) (Figure 1).
In analyses of cardiovascular diseases, higher genetically predicted
FGF21 concentration was strongly associated with a reduced risk of
venous thromboembolism, and had suggestive inverse associations with
coronary artery disease, heart failure, and ischemic stroke (Figure 2).
There was a suggestive association of higher genetically proxied FGF21
concentration with reduced risk of Alzheimer’s disease (based on
clinically diagnosed Alzheimer’s disease and Alzheimer’s disease by
proxy cases and their corresponding controls), but no association with
type 2 diabetes (Figure 2).