{"id":"1ea1b10d60c1","type":"article","url":"https://hartvaat.nl/2017/02/21/genetische-obesitas-en-risico-op-atriumfibrilleren-mendeliaanse-randomisatie/","title":"Genetische obesitas en risico op atriumfibrilleren: Mendeliaanse randomisatie","title_en":"Genetic Obesity and the Risk of Atrial Fibrillation: Causal Estimates from Mendelian Randomization.","category":"atriumfibrilleren","category_label":"Atriumfibrilleren","professions":["cardioloog","internist"],"tags":["obesitas"],"journal":"Circulation","doi":"10.1161/CIRCULATIONAHA.116.024921","source_url":"https://doi.org/10.1161/CIRCULATIONAHA.116.024921","authors":["Neal A Chatterjee","Franco Giulianini","Bastiaan Geelhoed","Kathryn L Lunetta","Jeffrey R Misialek","Maartje N Niemeijer","Michiel Rienstra","Lynda M Rose","Albert V Smith","Dan E Arking","Patrick T Ellinor","Jan Heeringa","Honghuang Lin","Steven A Lubitz","Elsayed Z Soliman","Niek Verweij","Alvaro Alonso","Emelia J Benjamin","Vilmundur Gudnason","Bruno H C Stricker","Pim Van Der Harst","Daniel I Chasman","Christine M Albert"],"significance":7,"published":"2017-02-21","source_date":"2017-02-21","image":"","kennis":["https://hartvaat.nl/kennis/atriumfibrilleren/chadsvasc-score/"],"congress":"","summary_en":"This Mendelian randomization study provided causal evidence that genetically determined higher BMI increases the risk of atrial fibrillation, establishing obesity as a modifiable causal risk factor for AF development.","created":"2026-07-03T10:26:34Z","updated":"2026-07-03T13:25:52Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Studie die met Mendeliaanse randomisatie causale schattingen biedt voor het verband tussen genetisch bepaalde obesitas en het risico op AF. Bevestigt obesitas als causale risicofactor voor boezemfibrilleren.","abstract_original":"BACKGROUND: Observational studies have identified an association between body mass index (BMI) and incident atrial fibrillation (AF). Inferring causality from observational studies, however, is subject to residual confounding, reverse causation, and bias. The primary objective of this study was to evaluate the causal association between BMI and AF by using genetic predictors of BMI. METHODS: We identified 51 646 individuals of European ancestry without AF at baseline from 7 prospective population-based cohorts initiated between 1987 and 2002 in the United States, Iceland, and the Netherlands with incident AF ascertained between 1987 and 2012. Cohort-specific mean follow-up ranged from 7.4 to 19.2 years, over which period there was a total of 4178 cases of incident AF. We performed a Mendelian randomization with instrumental variable analysis to estimate a cohort-specific causal hazard ratio for the association between BMI and AF. Two genetic instruments for BMI were used: FTO genotype (rs1558902) and a BMI gene score comprising 39 single-nucleotide polymorphisms identified by genome-wide association studies to be associated with BMI. Cohort-specific estimates were combined by random-effects, inverse variance-weighted meta-analysis. RESULTS: In age- and sex-adjusted meta-analysis, both genetic instruments were significantly associated with BMI (FTO: 0.43 [95% confidence interval, 0.32-0.54] kg/m2 per A-allele, P<0.001; BMI gene score: 1.05 [95% confidence interval, 0.90-1.20] kg/m2 per 1-U increase, P<0.001) and incident AF (FTO, hazard ratio, 1.07 [1.02-1.11] per A-allele, P=0.004; BMI gene score, hazard ratio, 1.11 [1.05-1.18] per 1-U increase, P<0.001). Age- and sex-adjusted instrumental variable estimates for the causal association between BMI and incident AF were hazard ratio, 1.15 (1.04-1.26) per kg/m2, P=0.005 (FTO) and 1.11 (1.05-1.17) per kg/m2, P<0.001 (BMI gene score). Both of these estimates were consistent with the meta-analyzed estimate between observed BMI and AF (age- and sex-adjusted hazard ratio 1.05 [1.04-1.06] per kg/m2, P<0.001). Multivariable adjustment did not significantly change findings. CONCLUSIONS: Our data are consistent with a causal relationship between BMI and incident AF. These data support the possibility that public health initiatives targeting primordial prevention of obesity may reduce the incidence of AF."}