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
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...
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Frontiers Media S.A.
2021-05-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fpubh.2021.584955/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nicole Probst-Hensch Nicole Probst-Hensch Ayoung Jeong Ayoung Jeong Daiana Stolz Marco Pons Paola M. Soccal Robert Bettschart Deborah Jarvis Deborah Jarvis John W. Holloway Florian Kronenberg Medea Imboden Medea Imboden Christian Schindler Christian Schindler Gianfranco F. Lovison Gianfranco F. Lovison Gianfranco F. Lovison |
spellingShingle |
Nicole Probst-Hensch Nicole Probst-Hensch Ayoung Jeong Ayoung Jeong Daiana Stolz Marco Pons Paola M. Soccal Robert Bettschart Deborah Jarvis Deborah Jarvis John W. Holloway Florian Kronenberg Medea Imboden Medea Imboden Christian Schindler Christian Schindler Gianfranco F. Lovison Gianfranco F. Lovison Gianfranco F. Lovison 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 Frontiers in Public Health Mendelian randomization body mass index genetic score lung function COPD longitudinal cohort |
author_facet |
Nicole Probst-Hensch Nicole Probst-Hensch Ayoung Jeong Ayoung Jeong Daiana Stolz Marco Pons Paola M. Soccal Robert Bettschart Deborah Jarvis Deborah Jarvis John W. Holloway Florian Kronenberg Medea Imboden Medea Imboden Christian Schindler Christian Schindler Gianfranco F. Lovison Gianfranco F. Lovison Gianfranco F. Lovison |
author_sort |
Nicole Probst-Hensch |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Public Health |
issn |
2296-2565 |
publishDate |
2021-05-01 |
description |
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. |
topic |
Mendelian randomization body mass index genetic score lung function COPD longitudinal cohort |
url |
https://www.frontiersin.org/articles/10.3389/fpubh.2021.584955/full |
work_keys_str_mv |
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doaj-5e92373d52b24e0880bc0df864963b0a2021-05-11T04:37:00ZengFrontiers Media S.A.Frontiers in Public Health2296-25652021-05-01910.3389/fpubh.2021.584955584955Causal 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 PerspectiveNicole Probst-Hensch0Nicole Probst-Hensch1Ayoung Jeong2Ayoung Jeong3Daiana Stolz4Marco Pons5Paola M. Soccal6Robert Bettschart7Deborah Jarvis8Deborah Jarvis9John W. Holloway10Florian Kronenberg11Medea Imboden12Medea Imboden13Christian Schindler14Christian Schindler15Gianfranco F. Lovison16Gianfranco F. Lovison17Gianfranco F. Lovison18Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, SwitzerlandDepartment of Public Health, University of Basel, Basel, SwitzerlandDepartment of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, SwitzerlandDepartment of Public Health, University of Basel, Basel, SwitzerlandClinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital Basel, Basel, SwitzerlandDivision of Pulmonary Medicine, Regional Hospital of Lugano, Lugano, SwitzerlandDivision of Pulmonary Medicine, Geneva University Hospitals, Geneva, SwitzerlandLungenpraxis Aarau, Hirslanden Klinik, Aarau, SwitzerlandMedical Research Council-Public Health England, Centre for Environment and Health, Imperial College London, London, United KingdomPopulation Health and Occupational Disease, National Heart and Lung Institute, Imperial College London, London, United KingdomHuman Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom0Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, SwitzerlandDepartment of Public Health, University of Basel, Basel, SwitzerlandDepartment of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, SwitzerlandDepartment of Public Health, University of Basel, Basel, SwitzerlandDepartment of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, SwitzerlandDepartment of Public Health, University of Basel, Basel, Switzerland1Department of Economics, Business and Statistics, University of Palermo, Palermo, ItalyObesity 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.https://www.frontiersin.org/articles/10.3389/fpubh.2021.584955/fullMendelian randomizationbody mass indexgenetic scorelung functionCOPDlongitudinal cohort |