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Causal effects of body mass index on airflow obstruction and forced mid-expiratory flow: a Mendelian randomization study taking interactions and age-specific instruments into consideration toward a life course perspective
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4646162
Author(s) Probst-Hensch, N.; Jeong, A.; Stolz, D.; Pons, M.; Soccal, P. M.; Bettschart, R.; Jarvis, D.; Holloway, J. W.; Kronenberg, F.; Imboden, M.; Schindler, C.; Lovison, G. F.
Author(s) at UniBasel Probst-Hensch, Nicole
Jeong, Ayoung
Imboden, Medea
Schindler, Christian
Lovison, Gianfranco
Year 2021
Title Causal effects of body mass index on airflow obstruction and forced mid-expiratory flow: a Mendelian randomization study taking interactions and age-specific instruments into consideration toward a life course perspective
Journal Front Public Health
Volume 9
Pages / Article-Number 584955
Keywords Copd; Mendelian randomization; body mass index; genetic score; longitudinal cohort; lung function; PanGas, Wenmann, Curetis, Boston Scientific, Cucassia, and also from Swiss Lung; Leagues. DS was paid for lectures including service on speaker's bureaus by the; following companies: Astra-Zeneca, Novartis, GSK, Roche, Zambon, Pfizer, Schwabe; Pharma and Vifor. The remaining authors declare that the research was conducted; in the absence of any commercial or financial relationships that could be; construed as a potential conflict of interest.
Mesh terms Adult; Age Factors; Body Mass Index; Cross-Sectional Studies; Female; Humans; Lung; Mendelian Randomization Analysis; Pulmonary Disease, Chronic Obstructive
Abstract Obesity has complex links to respiratory health. Mendelian randomization (MR) enables assessment of causality of body mass index (BMI) effects on airflow obstruction and mid-expiratory flow. In the adult SAPALDIA cohort, recruiting 9,651 population-representative samples aged 18-60 years at baseline (female 51%), BMI and the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) as well as forced mid-expiratory flow (FEF25-75%) were measured three times over 20 follow-up years. The causal effects of BMI in childhood and adulthood on FEV1/FVC and FEF25-75% were assessed in predictive (BMI averaged over 1st and 2nd, lung function (LF) averaged over 2nd and 3rd follow-up; N = 2,850) and long-term cross-sectional models (BMI and LF averaged over all follow-ups; N = 2,728) by Mendelian Randomization analyses with the use of weighted BMI allele score as an instrument variable and two-stage least squares (2SLS) method. Three different BMI allele scores were applied to specifically capture the part of BMI in adulthood that likely reflects tracking of genetically determined BMI in childhood. The main causal effects were derived from models containing BMI (instrumented by BMI genetic score), age, sex, height, and packyears smoked as covariates. BMI interactions were instrumented by the product of the instrument (BMI genetic score) and the relevant concomitant variable. Causal effects of BMI on FEV1/FVC and FEF25-75% were observed in both the predictive and long-term cross-sectional models. The causal BMI- LF effects were negative and attenuated with increasing age, and stronger if instrumented by gene scores associated with childhood BMI. This non-standard MR approach interrogating causal effects of multiplicative interaction suggests that the genetically rooted part of BMI patterns in childhood may be of particular relevance for the level of small airway function and airflow obstruction later in life. The methodological relevance of the results is first to point to the importance of a life course perspective in studies on the etiological role of BMI in respiratory health, and second to point out novel methodological aspects to be considered in future MR studies on the causal effects of obesity related phenotypes.
ISSN/ISBN 2296-2565 (Electronic)2296-2565 (Linking)
URL https://doi.org/10.3389/fpubh.2021.584955
edoc-URL https://edoc.unibas.ch/89292/
Full Text on edoc Available
Digital Object Identifier DOI 10.3389/fpubh.2021.584955
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/34046380
ISI-Number WOS:000653446000001
Document type (ISI) Journal Article
 
   

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