Mendelian randomization suggests a bidirectional, causal relationship between physical inactivity and adiposity

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Carrasquilla, Germán DNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (författare)

Mendelian randomization suggests a bidirectional, causal relationship between physical inactivity and adiposity

Artikel/kapitelEngelska2022

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eLife Sciences Publications Ltd,2022
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LIBRIS-ID:oai:DiVA.org:uu-472104
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-472104URI
https://doi.org/10.7554/eLife.70386DOI

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Språk:engelska
Sammanfattning på:engelska

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Physical inactivity and increased sedentary time are associated with excess weight gain in observational studies. However, some longitudinal studies indicate reverse causality where weight gain leads to physical inactivity and increased sedentary time. As observational studies suffer from reverse causality, it is challenging to assess the true causal directions. Here, we assess the bidirec- tional causality between physical inactivity, sedentary time, and adiposity by bidirectional Mendelian randomization analysis. We used results from genome-wide association studies for accelerometer- based physical activity and sedentary time in 91,105 individuals and for body mass index (BMI) in 806,834 individuals. We implemented Mendelian randomization using CAUSE method that accounts for pleiotropy and sample overlap using full genome-wide data. We also applied inverse variance- weighted, MR-Egger, weighted median, and weighted mode methods using genome-wide signif- icant variants only. We found evidence of bidirectional causality between sedentary time and BMI: longer sedentary time was causal for higher BMI [beta (95% CI) from CAUSE method: 0.11 (0.02, 0.2), p = 0.02], and higher BMI was causal for longer sedentary time (0.13 (0.08, 0.17), p = 6.3 x 10-4). Our analyses suggest that higher moderate and vigorous physical activity are causal for lower BMI (moderate: –0.18 (-0.3,–0.05), p = 0.006; vigorous: –0.16 (-0.24,–0.08), p = 3.8 × 10-4), but indicate that the association between higher BMI and lower levels of physical activity is due to hori- zontal pleiotropy. The bidirectional, causal relationship between sedentary time and BMI suggests that decreasing sedentary time is beneficial for weight management, but also that targeting adiposity may lead to additional health benefits by reducing sedentary time.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
physical activity
mendelian randomization analysis
human genetics
cardiometabolic risk factors
obesity
causality

Biuppslag (personer, institutioner, konferenser, titlar ...)

García-Ureña, MarioNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (författare)
Fall, Tove,1979-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi,Tove Fall(Swepub:uu)tovfa878 (författare)
Sørensen, Thorkild IANovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (författare)
Kilpeläinen, Tuomas ONovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (författare)
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkScience for Life Laboratory, SciLifeLab (creator_code:org_t)

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Ingår i:eLIFE: eLife Sciences Publications Ltd112050-084X

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Av författaren/redakt...: Carrasquilla, Ge ...; García-Ureña, Ma ...; Fall, Tove, 1979 ...; Sørensen, Thorki ...; Kilpeläinen, Tuo ...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Endokrinologi oc ...

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