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Relationships between obesity and functional outcome after ischemic stroke: a Mendelian randomization study

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Abstract

Background and objectives

Most previous studies suggested obesity deteriorates the functional outcome after ischemic stroke. But there are researches claiming that obesity is associated with lower mortality, recurrence, and readmission rates, which is known as the obesity paradox. Our current research aimed to investigate the correlation between genetically obesity and the post-stroke outcome with the Mendelian randomization (MR) method.

Methods

The UK Biobank and the GIANT consortium provided instrumental variables for body mass index (BMI, 806,834 individuals) and waist-to-hip ratio (WHR, 697,734 individuals). Data of functional outcome after ischemic stroke were obtained from the Genetics of Ischemic Stroke Functional Outcome network (6012 individuals). Inverse-variance weighted approach was utilized as the primary analyses. Sensitivity analyses involved the utilization of different MR methods. The heterogeneity among genetic variants was assessed by I2 and Q value statistics.

Results

In univariable analysis, there was a significant connection between genetic susceptibility to WHR and worse functional outcome (modified Rankin Scale 3) after ischemic stroke (OR [95%CI] = 1.47 [1.07, 2.02], P = 0.016).

Genetic liability to BMI and was not associated with post-stroke functional outcome (all P > 0.05). The overall patterns between genetic liability to WHR and functional outcome post-ischemic outcome no longer existed in the multivariable MR analysis after adjusting for BMI (OR [95%CI] = 1.26[0.76,1.67], P = 0.56).

Conclusion

The current MR study provided evidence that WHR was correlated to unfavorable outcome post-ischemic stroke. Exploring interventions against obesity may potentially improve recovery after ischemic stroke.

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Data availability

The datasets generated during and analyzed during the current study are available in the GIANT and UK Biobank (https://portals.broadinstitute.org/collaboration/giant/index.php/GIANT_consortium_data_files), UK Biobank (https://www.ukbiobank.ac.uk/), and GISCOME network (https://cd.hugeamp.org/downloads.html).

Abbreviations

BMI :

Body mass index

CI :

Confidence intervals

GIANT :

Genetic Investigation of ANthropometric Traits

GISCOME :

Genetics of Ischemic Stroke Functional Outcome

HC :

Hip circumference

IVW :

Inverse-variance weighted

MR :

Mendelian randomization

MR-PRESSO :

Mendelian Randomization Pleiotropy Residual Sum and Outlier

mRS :

Modified Rankin Scale

NIHSS :

NIH Stroke score

OR :

Odd ratio

preVAT :

Predicted visceral adipose tissue

SNPs :

Single nucleotide polymorphisms

WC :

Waist circumference

WHR :

Waist-to-hip ratio

WHRadjBMI :

Waist-to-hip ratio adjusted body mass index

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Acknowledgements

We thank UK Biobank, GIANT consortium, and GISCOME network for providing summary statistics data for the analyses. We also thank the BioRender website for material which is necessary for the flowchart.

Funding

This work is supported by grants from National Natural Science Foundation of China (No. 8271282) and Health Youth Backbone Project of Suzhou City (Qngg2021003) to Juehua Zhu. This work is also supported by grants from General Project of National Natural Science Foundation of China (No.82071300), Introduction of Clinical Medicine Team project in Suzhou (SZYJTD201802), and Suzhou Gusu Health Talents Program Training Project (GSWS2020002) to Qi Fang.

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, China

    Jieyi Lu, Siqi Gong, Juehua Zhu & Qi Fang

  2. Medical College of Soochow University, 199 Renai Road, Suzhou, 215123, China

    Jieyi Lu & Siqi Gong

  3. Department of Neurology, Dushu Lake Hospital Affiliated to Soochow University, 9 Chongwen Road, Suzhou, 215125, China

    Qi Fang

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Contributions

All authors contributed to the study conception and design. Data curation, writing, and analysis were performed by Jieyi Lu and Siqi Gong. The first draft of the manuscript was written by Juehua Zhu and Qi Fang, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Juehua Zhu or Qi Fang.

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As in the STROBE-MR Statement, Mendelian Randomization is a method that uses genetic variation to strengthen possible causal inference regarding modifiable exposures influencing risk of disease or other outcomes. Our MR study is implemented within an instrumental variable framework, using genetic variants as instrumental variables, and it does not require individual-level data. The Institutional Review Board of The First Affiliated Hospital of Soochow University has confirmed that no ethical approval is required.

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Jieyi Lu and Siqi Gong have contributed equally to this work and share the first authorship.

Qi Fang and Juehua Zhu contributed equally as corresponding authors.

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Lu, J., Gong, S., Zhu, J. et al. Relationships between obesity and functional outcome after ischemic stroke: a Mendelian randomization study. Neurol Sci (2024). https://doi.org/10.1007/s10072-024-07415-w

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