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- Title
Associations of common genetic variants with age-related changes in fasting and postload glucose: evidence from 18 years of follow-up of the Whitehall II cohort.
- Authors
Jensen AC; Barker A; Kumari M; Brunner EJ; Kivimäki M; Hingorani AD; Wareham NJ; Tabák AG; Witte DR; Langenberg C; Jensen, Anders C; Barker, Adam; Kumari, Meena; Brunner, Eric J; Kivimäki, Mika; Hingorani, Aroon D; Wareham, Nicholas J; Tabák, Adam G; Witte, Daniel R; Langenberg, Claudia
- Abstract
<bold>Objective: </bold>In the general, nondiabetic population, fasting glucose increases only slightly over time, whereas 2-h postload glucose shows a much steeper age-related rise. The reasons underlying these different age trajectories are unknown. We investigated whether common genetic variants associated with fasting and 2-h glucose contribute to age-related changes of these traits.<bold>Research Design and Methods: </bold>We studied 5,196 nondiabetic participants of the Whitehall II cohort (aged 40-78 years) attending up to four 5-yearly oral glucose tolerance tests. A genetic score was calculated separately for fasting and 2-h glucose, including 16 and 5 single nucleotide polymorphisms, respectively. Longitudinal modeling with age centered at 55 years was used to study the effects of each genotype and genetic score on fasting and 2-h glucose and their interactions with age, adjusting for sex and time-varying BMI.<bold>Results: </bold>The fasting glucose genetic score was significantly associated with fasting glucose with a 0.029 mmol/L (95% CI 0.023-0.034) difference (P = 2.76 × 10(-21)) per genetic score point, an association that remained constant over time (age interaction P = 0.17). Two-hour glucose levels differed by 0.076 mmol/L (0.047-0.105) per genetic score point (P = 3.1 × 10(-7)); notably, this effect became stronger with increasing age by 0.006 mmol/L (0.003-0.009) per genetic score point per year (age interaction P = 3.0 × 10(-5)), resulting in diverging age trajectories by genetic score.<bold>Conclusions: </bold>Common genetic variants contribute to the age-related rise of 2-h glucose levels, whereas associations of variants for fasting glucose are constant over time, in line with stable age trajectories of fasting glucose.
- Publication
Diabetes, 2011, Vol 60, Issue 5, p1617
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db10-1393