title: Genetic variants associated with type 2 diabetes and adiposity and risk of intracranial and abdominal aortic aneurysms.
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.
authors.affiliation: Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Femke Ng
authors.initials: FN
authors.lastname: van 't Hof
authors.affiliation: Department of Internal Medicine, Lausanne University Hospital, Switzerland, Switzerland.
authors.forename: Julien
authors.initials: J
authors.lastname: Vaucher
authors.affiliation: Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.|Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, UK.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Holmes
authors.affiliation: Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Arno
authors.initials: A
authors.lastname: de Wilde
authors.affiliation: Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Annette F
authors.initials: AF
authors.lastname: Baas
authors.affiliation: Department of Vascular Surgery, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Jan D
authors.initials: JD
authors.lastname: Blankensteijn
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: Lambertus Alm
authors.initials: LA
authors.lastname: Kiemeney
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: Sita H
authors.initials: SH
authors.lastname: Vermeulen
authors.affiliation: Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Gabriël Je
authors.initials: GJ
authors.lastname: Rinkel
authors.affiliation: Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Paul Iw
authors.initials: PI
authors.lastname: de Bakker
authors.affiliation: Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ynte M
authors.initials: YM
authors.lastname: Ruigrok
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000453:epidemiology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D002532:Intracranial Aneurysm / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide