Abstract
Epidemiological studies show that type 2 diabetes (T2D) is inversely associated with intracranial aneurysms (IA) and abdominal aortic aneurysms (AAA). Although adiposity has not been considered a risk factor for IA, there have been inconsistent reports relating adiposity to AAA risk. We assessed whether these observations have a genetic, causal basis. To this end, we extracted genotypes of validated single-nucleotide polymorphisms associated with T2D (n=65), body mass index (BMI) (n=97) and waist–hip ratio adjusted for BMI (WHRadjBMI) (n=47) from genotype data collected in 717 IA cases and 1988 controls, and in 818 AAA cases and 3004 controls, all of Dutch descent. For each of these three traits, we computed genetic risk scores (GRS) for each individual in these case–control data sets by summing the number of risk alleles weighted by their published effect size, and tested whether these GRS were associated with risk of aneurysm. We divided the cohorts into GRS quartiles, and compared IA and AAA risk in the highest with the lowest GRS quartile using logistic regression. We found no evidence for association in IA or AAA risk between top and bottom quartiles for the genetic risk scores for T2D, BMI and WHRadjBMI. However, additional Mendelian randomization analyses suggested a trend to potentially causal associations between BMI and WHRadjBMI and risk of AAA. Overall, our results do not support epidemiological observations relating T2D to aneurysm risk, but may indicate a potential role of adiposity in AAA that requires further investigation.
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Acknowledgements
FNGVH is supported by a grant of the Dutch Heart Foundation (NHS) (project no. 2008B004). JV works for the CoLaus|PsyCoLaus study which was and is supported by research grants from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (grants 3200B0-105993, 3200B0-118308, 33CSCO-122661, 33CS30-139468 and 33CS30-148401). YMR is supported by a clinical fellowship grant of the Netherlands Organization for Scientific Research (NWO) (project no. 40-00703-98-13533). AFB is supported by a grant from the Dr E Dekker Program of the NHS (2009T001). The generation of the GWAS data sets is supported by the Netherlands Organisation for Scientific Research NWO Investments (no. 175.010.2005.011, 911-03-012), the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA), project no. 050-060-810. The Rotterdam Study is funded by the Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sport, the European Commission (DG XII) and the Municipality of Rotterdam.
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van 't Hof, F., Vaucher, J., Holmes, M. et al. Genetic variants associated with type 2 diabetes and adiposity and risk of intracranial and abdominal aortic aneurysms. Eur J Hum Genet 25, 758–762 (2017). https://doi.org/10.1038/ejhg.2017.48
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DOI: https://doi.org/10.1038/ejhg.2017.48
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