Summary
A medRxiv preprint reports genetic evidence that higher BMI increases HbA1c and random glucose in African- and European-ancestry groups in UK Biobank. Estimates for African-American and Ugandan groups in a separate analysis were less precise.
A medRxiv preprint reports genetic evidence that higher body mass index (BMI) increases glycated haemoglobin (HbA1c) and random glucose in adults of African and European ancestry. In its main UK Biobank analyses, the estimated effects were similar across the two groups. A separate multi-ancestry analysis found less precise HbA1c estimates for African-American and Ugandan participants.
The study used Mendelian randomization, a method that uses genetic variants associated with an exposure—in this case BMI—as proxies to estimate its effects on an outcome. It can help address some sources of confounding in conventional observational studies, but its estimates depend on assumptions about how the genetic variants relate to the exposure and outcome. This is a preprint, so the findings have not yet been peer reviewed.
How the study compared populations
The researchers conducted a two-sample Mendelian randomization analysis. To build BMI instruments, they used genetic data from 10,476 African adults in the AWI-Gen study and a European BMI genome-wide association study of about 700,000 people. Of 428 independent variants associated with BMI, 363 had the same direction of effect in both populations and were used as instruments.
The main outcome data came from UK Biobank: HbA1c results covered 5,790 participants of African ancestry and 400,825 of European ancestry; random-glucose results covered 5,750 and 314,916, respectively. The primary analysis used the inverse-variance-weighted method. The authors also ran MR-Egger, weighted-median and weighted-mode sensitivity analyses, which they said suggested the results were not biased by unbalanced horizontal pleiotropy—a situation in which genetic variants affect an outcome through pathways other than BMI.
What the estimates show
In UK Biobank, each 1 standard deviation (SD) higher genetically predicted BMI was associated with 0.26 SD higher HbA1c in the African-ancestry group (95% confidence interval [CI] 0.07 to 0.45) and 0.27 SD higher HbA1c in the European-ancestry group (95% CI 0.22 to 0.32). For random glucose, the corresponding estimates were 0.21 SD (95% CI 0.03 to 0.37) and 0.15 SD (95% CI 0.12 to 0.18).
The additional MAGIC analysis used different units: percentage-point changes in HbA1c per 1 SD higher BMI. Its estimate for Europeans was 0.04% (95% CI 0.02 to 0.05). Estimates for African Americans, 0.01% (95% CI −0.05 to 0.07), and Ugandans, −0.02% (95% CI −0.10 to 0.05), had confidence intervals spanning zero. The study included 6,647 African-American and 4,441 Ugandan participants in this analysis.
Taken together, the UK Biobank findings support broadly similar BMI effects on these glycaemic traits across the two ancestry groups studied. The less precise MAGIC estimates for African-American and Ugandan participants underline the need for larger studies of glycaemic traits in African and other non-European populations, as the authors note. The results concern genetic estimates at the population level; they are not individual predictions of how a person's blood glucose will change.