A critical evaluation of results from genome-wide association studies of micronutrient status and their utility in the practice of precision nutrition

Abstract

Rapid advances in ‘omics’ technologies have paved the way forward to an era where more ‘precise’ approaches – ‘precision’ nutrition – which leverage data on genetic variability alongside the traditional indices, have been put forth as the state-of-the-art solution to redress the effects of malnutrition across the life course. We purport that this inference is premature and that it is imperative to first review and critique the existing evidence from large-scale epidemiological findings. We set out to provide a critical evaluation of findings from genome-wide association studies (GWAS) in the roadmap to precision nutrition, focusing on GWAS of micronutrient disposition. We found that a large number of loci associated with biomarkers of micronutrient status have been identified. Mean estimates of heritability of micronutrient status ranged between 20 and 35 % for minerals, 56–59 % for water-soluble and 30–70 % for fat-soluble vitamins. With some exceptions, the majority of the identified genetic variants explained little of the overall variance in status for each micronutrient, ranging between 1·3 and 8 % (minerals), <0·1–12 % (water-soluble) and 1·7–2·3 % for (fat-soluble) vitamins. However, GWAS have provided some novel insight into mechanisms that underpin variability in micronutrient status. Our findings highlight obvious gaps that need to be addressed if the full scope of precision nutrition is ever to be realised, including research aimed at (i) dissecting the genetic basis of micronutrient deficiencies or ‘response’ to intake/supplementation (ii) identifying trans-ethnic and ethnic-specific effects (iii) identifying gene–nutrient interactions for the purpose of unravelling molecular ‘behaviour’ in a range of environmental contexts.

Personalized Nutrition for Management of Micronutrient Deficiency—Literature Review in Non-bariatric Populations and Possible Utility in Bariatric Cohort

“…The ability to identify a person having genetic variants involved in vitamin and mineral metabolism may reduce the chance of developing micronutrient deficiencies that can lead to various diseases [19]. GWAS have shown that several genetic variants associated with vitamin metabolism can affect circulating vitamin levels, which could lead to abnormal vitamin function [24]. Most GWAS have been conducted among healthy, Caucasian populations, which is a limitation in this research [24].…”

“…GWAS have shown that several genetic variants associated with vitamin metabolism can affect circulating vitamin levels, which could lead to abnormal vitamin function [24]. Most GWAS have been conducted among healthy, Caucasian populations, which is a limitation in this research [24]. Table 1 demonstrates recent studies that associate genetic variants and micronutrient metabolism.…”

Vitamin B12status in health and disease: a critical review. Diagnosis of deficiency and insufficiency – clinical and laboratory pitfalls

“…More common effects of genetic variation in B 12 levels can be described by its heritability (h 2 ) in different populations as well as associations between specific polymorphisms in genes and the various indicators of B 12 status. Dib et al [65] have provided robust h 2 estimates for all markers of vitamin B 12 status for UK-based Caucasian populations that range from $15% in the case of MMA right up to $80% for holoTC, highlighting that B 12 status is a complex and multifactorial trait, whereby several polymorphisms in multiple genes interact with the environment to cause variable B 12 status. So far, candidate gene and genomewide association studies (GWAS) have identified $59 SNPs from 19 genes involved in cobalamin metabolism and various indicators of its status [66].…”

From personalised nutrition to precision medicine: the rise of consumer genomics and digital health

“…Related to nutrition status, and equally suspect in terms of predictive validity, is personalised nutrition advice from multiple companies claiming to help consumers maintain healthy levels of vitamins, antioxidants and minerals, on the basis of a handful of genetic variants. In contrast to obesity and type 2 diabetes, to date much fewer loci have been associated with the biomarkers of micronutrient status (60) . These explain only a small fraction of variance in micronutrient status.…”

“…Notably, while scientists have remained largely circumspect about clinical utility and the extent to which genetic or polygenic risk scores can explain overall risk for common, multifactorial diseases (e.g. obesity, diabetes, fatty liver) or micronutrient status (59,60) ; an astonishing number of direct-to-consumer (DTC) genetic testing companies have proliferated offering personalised nutrition advice to individuals based on nutrigenetic testing via the Internet (61) .

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