Tier 4 — mechanistic

Assessing the causal association of glycine with risk of cardio-metabolic diseases

Wittemans LBL, Lotta LA, Oliver-Williams C, Stewart ID, Surendran P, Karthikeyan S, Day FR, Koulman A, Imamura F, Zeng L, Erdmann J, Schunkert H, Khaw KT, Griffin JL, Forouhi NG, Scott RA, Wood AM, Burgess S, Howson JMM, Danesh J, Wareham NJ, Butterworth AS, Langenberg C
Nature communications 2019 10(1):1060

Bibliography

PubMed
PMID 30837465
PubMed Central
PMC6400990
DOI
10.1038/s41467-019-08936-1
Funding
Indexed support: Biotechnology and Biological Sciences Research Council; Medical Research Council; National Institute for Health Research (NIHR); British Heart Foundation; Cancer Research UK; Wellcome Trust; European Research Council. See the publication for grant and funder details.
Competing interests
Disclosures include pharmaceutical-company employment, shareholding, grants or fees for some authors; see the original declaration for individual details.

Study snapshot

DesignHuman genetic association and Mendelian-randomization analyses
ModelAdult humans
SampleGWAS meta-analysis of 80,003 participants, with cardiometabolic outcome datasets
InterventionGenetic instruments for circulating glycine; no administered supplement
DurationGenetic epidemiology; no dosing period
EndpointsCoronary heart disease; Type 2 diabetes; Blood pressure; Reverse genetic effects of insulin resistance

What the study showed, in plain terms

The genetic analyses supported a possible protective relationship between glycine and coronary disease. They also suggested that insulin resistance can lower glycine, complicating claims that glycine deficiency causes diabetes.

Key findings

  • Twenty-seven glycine-associated loci were identified.
  • Coronary-disease evidence was stronger than type 2 diabetes evidence.
  • Reverse-direction analyses linked hyperinsulinemia with lower glycine.

What this study can and cannot tell us

Mendelian-randomization estimates depend on valid instruments and pleiotropy assumptions.

Conflicting later genetic studies should be considered; the analysis does not specify an effective supplement dose.

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Editorial review

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction