Journal
EUROPEAN HEART JOURNAL
Volume 29, Issue 20, Pages 2552-2560Publisher
OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/ehn252
Keywords
Atherosclerosis; Body mass index; Mendelian randomization; Variation (genetics)
Categories
Funding
- Academy of Finland [77841, 34316, 210283, 117941, 117604, 124322]
- Social Insurance Institution of Finland
- Finnish Work Environment Foundation
- Turku University Foundation
- Juho Vainio Foundation
- Finnish Foundation of Cardiovascular Research
- Finnish Cultural Foundation, Finland
- UK Department of Health Career Scientist Award
- Research Foundation of Tampere University Hospital
- Tampere University Hospital
- Turku University Central Hospital.
- Wellcome Trust Research Fellow
- MRC [G0600705, MC_U130059821] Funding Source: UKRI
- British Heart Foundation [RG/07/008/23674] Funding Source: researchfish
- Medical Research Council [MC_U130059821, G8802774, G0600705, G0100222, G19/35] Funding Source: researchfish
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Alms Mendelian randomization uses genetic variants related to environmentally modifiable risk factors in an attempt to improve causal inference from observational data. We examined the effect of lifetime body mass index (BMI) on adult carotid intima-media thickness (CIMT) and various atherosclerotic risk factors by using both Mendelian randomization and conventional analyses. Methods and results A total of 2230 individuals (1218 women), aged 3-18 at study induction, took part in clinical examinations in 1980, 1983, 1986, and, most recently, 2001 when they were aged 24-39. In these analyses we utilized the known relation between FTO polymorphism rs9939609 and BMI. The dose-response association between the number of A alleles in FTO and higher mean BMI from childhood to adulthood was confirmed, but no associations with potential confounding factors were observed. In standard regression models, lifetime BMI was associated with adult CIMT, lifetime systolic blood pressure, adult fasting glucose, and adult HOMA-index. When variation in FTO was used as an instrument for unconfounded BMI levels, similar or larger effects of lifetime BMI on all these phenotypes were found, although with wider confidence intervals. Conclusion Mutually supportive results from Mendelian randomization and standard regression models strengthen the evidence of the effect of lifetime BMI on atherosclerosis risk in young adults.
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