A new cross-platform meta-analysis of genome-wide association studies for glycine in more than 80,000 participants, led by Dr Claudia Langenberg and PhD student Laura Wittemans of our Aetiology of Diabetes Programme, and published today in Nature Communications, identified 27 genetic variants that were associated with circulating glycine levels, including 22 that have not previously been reported, and together explaining more than 15% of the variance in glycine.
While earlier epidemiological studies have found that higher circulating levels of glycine are associated with lower incidence of myocardial infarction and type 2 diabetes (T2D), it has not been clear if this association reflects a causal, protective effect of glycine. The analyses undertaken by Wittemans and colleagues, published in Nature Communications, indicate that glycine is genetically associated with lower coronary heart disease (CHD) risk, and that this association may be mediated by a blood pressure-lowering effect of glycine.
The researchers also found slightly weaker evidence for a genetic association of glycine with lower risk of T2D, and their finding of a strong association between genetically predicted hyperinsulinaemia and lower levels of glycine, indicates that the consistently observed association between higher glycine and lower incidence of T2D may be driven by a causal effect of insulin resistance on glycine.
This research highlights the role of the glycine pathway as a potential, novel aetiological pathway to CHD and identifies insulin resistance as a potential cause of low circulating levels of glycine.
- ‘Assessing the causal association of glycine with risk of cardio-metabolic diseases’ by Wittemans et al. Nat Commun, 05 January 2019. https://www.doi.org/ 10.1038/s41467-019-08936-1