Genetic variants associated with type 2 diabetes and adiposity and risk of intracranial and abdominal aortic aneurysms

Autor: Arno de Wilde, Ynte M. Ruigrok, Albert Hofman, André G. Uitterlinden, Julien Vaucher, Femke N G van 't Hof, Paul I.W. de Bakker, Lambertus A. Kiemeney, Michael V. Holmes, Gabriel J.E. Rinkel, Jan D. Blankensteijn, Fernando Rivadeneira, Sita H. Vermeulen, Annette F. Baas
Přispěvatelé: Epidemiology, Internal Medicine, Surgery, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Type 2 diabetes
Logistic regression
Research Support
Polymorphism
Single Nucleotide
Article
03 medical and health sciences
Aneurysm
SDG 3 - Good Health and Well-being
Internal medicine
Epidemiology
Mendelian randomization
medicine
Diabetes Mellitus
Journal Article
Genetics
Humans
Abdominal
Genetics(clinical)
Genetic Predisposition to Disease
cardiovascular diseases
Risk factor
Polymorphism
Non-U.S. Gov't
Genetics (clinical)
Adiposity
Aged
business.industry
Research Support
Non-U.S. Gov't
Intracranial Aneurysm
Single Nucleotide
Middle Aged
medicine.disease
Aortic Aneurysm
030104 developmental biology
Quartile
Diabetes Mellitus
Type 2
Urological cancers Radboud Institute for Health Sciences [Radboudumc 15]
cardiovascular system
Female
business
Body mass index
Type 2
Aortic Aneurysm
Abdominal
Zdroj: European Journal of Human Genetics, 25(6), 758-762. Nature Publishing Group
van 't Hof, F NG, Vaucher, J, Holmes, M V, de Wilde, A, Baas, A F, Blankensteijn, J D, Hofman, A, Kiemeney, L ALM, Rivadeneira, F, Uitterlinden, A G, Vermeulen, S H, Rinkel, G JE, de Bakker, P IW & Ruigrok, Y M 2017, ' Genetic variants associated with type 2 diabetes and adiposity and risk of intracranial and abdominal aortic aneurysms ', European Journal of Human Genetics, vol. 25, no. 6, pp. 758-762 . https://doi.org/10.1038/ejhg.2017.48
European Journal of Human Genetics, 25, 758-762
European Journal of Human Genetics, 25(6), 758. Nature Publishing Group
European Journal of Human Genetics, 25, 6, pp. 758-762
ISSN: 1018-4813
Popis: 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.European Journal of Human Genetics advance online publication, 5 April 2017; doi:10.1038/ejhg.2017.48.
Databáze: OpenAIRE
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