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The unique challenges of studying the genetics of diet and nutrition

Nature Medicine volume 28, pages 221–222 (2022)Cite this article

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To the Editor — Nutrition science has faced a long-standing challenge of establishing causality for nutritional exposures with chronic health outcomes. In the absence of long-term tightly controlled intervention trials, researchers rely on observational studies — where difficulties in measuring food intake and confounding from other behaviors and environmental factors undermine certainty of the evidence. Many would therefore agree that nutrition science is overdue for a renovation.

In MR, a genetic variant serves as a valid instrument for an exposure under certain conditions, including that the genetic variant is associated with the exposure, does not share common causes with the health outcome, and affects the outcome only through its effect on the exposure of interest2. It is proposed that if these assumptions hold, then a genetic variant for an exposure acts similarly to randomized treatment allocation in a randomized clinical trial. However, changes in habitual diet over time — sudden or gradual — are one reason nutritional exposures pose unique challenges to the MR framework.

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Fig. 1: Main methodological considerations of MR studies when implemented for nutritional exposures.

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Acknowledgements

We thank S. Swanson (Erasmus University Rotterdam) and J. Speakman (University of Aberdeen) for their thoughtful contributions to earlier versions of the manuscript. Funding was received from National Institutes of Health grant P30DK40561 (J.M.) and American Diabetes Association grant no. 7-21-JDFM-005 (J.M.).

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Authors and Affiliations

  1. Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA

    Jordi Merino

  2. Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Jordi Merino

  3. Department of Medicine, Harvard Medical School, Boston, MA, USA

    Jordi Merino

  4. Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Deirdre K. Tobias

  5. Nutrition Department, Harvard TH Chan School of Public Health, Boston, MA, USA

    Deirdre K. Tobias

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  1. Jordi Merino
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  2. Deirdre K. Tobias
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J.M. and D.K.T. contributed to the original draft and editing of the manuscript.

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Correspondence to Deirdre K. Tobias.

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The authors declare no competing interests.

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Merino, J., Tobias, D.K. The unique challenges of studying the genetics of diet and nutrition. Nat Med 28, 221–222 (2022). https://doi.org/10.1038/s41591-021-01626-w

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