Special Issue "Mendelian Randomization Studies on Nutritional Factors and Health Outcomes"

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutritional Epidemiology".

Deadline for manuscript submissions: closed (10 March 2022) | Viewed by 10994

Special Issue Editor

Dr. Susanna C. Larsson
E-Mail Website
Guest Editor
Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-17177 Stockholm, Sweden
Interests: diet; lifestyle; modifiable risk factors; stroke; cardiovascular disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Poor diet is a leading cause of morbidity and mortality. However, the causal role of specific foods, nutrients, and other dietary compounds in health and disease is not fully established, as most evidence derives from traditional observational studies. Such studies are susceptible to residual confounding, reverse causation bias, and misclassification of dietary intake. Mendelian randomization is a method that can reduce such biases in observational studies and provide more robust evidence concerning the role of dietary factors in health and disease.

The present Special Issue aims to add research knowledge from Mendelian randomization studies on nutritional factors in relation to health outcomes, including diseases and risk factors (e.g., hypertension, elevated blood lipids, and adiposity) that may mediate the diet–disease associations. This issue welcomes original and review articles reporting results from Mendelian randomization studies.

Dr. Susanna C. Larsson
Guest Editor

Manuscript Submission Information

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Keywords

  • mendelian randomization
  • single nucleotide polymorphisms
  • beverages
  • foods
  • nutrients
  • vitamins
  • minerals
  • fatty acids

Published Papers (9 papers)

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Editorial

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Editorial
Mendelian Randomization Studies on Nutritional Factors and Health Outcomes
Nutrients 2022, 14(14), 2780; https://doi.org/10.3390/nu14142780 - 06 Jul 2022
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Abstract
Poor diet is a leading cause of morbidity and mortality [...] Full article

Research

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Communication
Plasma Caffeine Levels and Risk of Alzheimer’s Disease and Parkinson’s Disease: Mendelian Randomization Study
Nutrients 2022, 14(9), 1697; https://doi.org/10.3390/nu14091697 - 19 Apr 2022
Cited by 1 | Viewed by 1933
Abstract
We leveraged genetic variants associated with caffeine metabolism in the two-sample Mendelian randomization framework to investigate the effect of plasma caffeine levels on the risk of Alzheimer’s disease and Parkinson’s disease. Genetic association estimates for the outcomes were obtained from the International Genomics [...] Read more.
We leveraged genetic variants associated with caffeine metabolism in the two-sample Mendelian randomization framework to investigate the effect of plasma caffeine levels on the risk of Alzheimer’s disease and Parkinson’s disease. Genetic association estimates for the outcomes were obtained from the International Genomics of Alzheimer’s Project, the International Parkinson’s Disease Genomics consortium, the FinnGen consortium, and the UK Biobank. Genetically predicted higher plasma caffeine levels were associated with a non-significant lower risk of Alzheimer’s disease (odds ratio 0.87; 95% confidence interval 0.76, 1.00; p = 0.056). A suggestive association was observed for genetically predicted higher plasma caffeine levels and lower risk of Parkinson’s disease in the FinnGen consortium. but not in the International Parkinson’s Disease Genomics consortium; no overall association was found (odds ratio 0.92; 95% confidence interval 0.77, 1.10; p = 0.347). This study found possible suggestive evidence of a protective role of caffeine in Alzheimer’s disease. The association between caffeine and Parkinson’s disease requires further study. Full article
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Article
Alcohol, Coffee, and Milk Intake in Relation to Epilepsy Risk
Nutrients 2022, 14(6), 1153; https://doi.org/10.3390/nu14061153 - 09 Mar 2022
Cited by 1 | Viewed by 1124
Abstract
Alcohol, coffee and milk intakes have been explored in relation to epilepsy risk in observational studies; however, the results were not consistent. We performed a Mendelian randomisation (MR) study to evaluate the causality of these relationships. Genetic variants associated with alcohol, coffee and [...] Read more.
Alcohol, coffee and milk intakes have been explored in relation to epilepsy risk in observational studies; however, the results were not consistent. We performed a Mendelian randomisation (MR) study to evaluate the causality of these relationships. Genetic variants associated with alcohol, coffee and milk intake were adopted as instrumental variables. We obtained the summary data of epilepsy from the International League Against Epilepsy (ILAE) Consortium (15,212 cases and 29,677 controls) and FinnGen consortium (4588 cases and 144,780 controls). Genetically predicted alcohol intake was associated with a higher risk of epilepsy in the ILAE Consortium (odds ratio (OR): 1.22, 95% confidence intervals (CI): 1.02–1.45). The association in the FinnGen consortium remained consistent in direction. Combined analysis of ILAE and FinnGen databases further indicated that genetically predicted alcohol intake was associated with a higher risk of epilepsy (OR = 1.24; 95% CI, 1.06–1.47, p = 0.009). Genetically predicted coffee intake was not related to epilepsy risk, while higher genetically predicted milk intake was related to a lower risk of epilepsy (OR = 0.957; 95% CI, 0.917–0.999, p = 0.044). Our results suggest a detrimental effect of alcohol intake on the risk of epilepsy, while milk intake might be associated with a decreased risk of epilepsy. Full article
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Article
Dietary-Derived Essential Nutrients and Amyotrophic Lateral Sclerosis: A Two-Sample Mendelian Randomization Study
Nutrients 2022, 14(5), 920; https://doi.org/10.3390/nu14050920 - 22 Feb 2022
Cited by 1 | Viewed by 1128
Abstract
Previous studies have suggested a close but inconsistent relationship between essential nutrients and the risk of amyotrophic lateral sclerosis (ALS), and whether this association is causal remains unknown. We aimed to investigate the potential causal relation between essential nutrients (essential amino acids, essential [...] Read more.
Previous studies have suggested a close but inconsistent relationship between essential nutrients and the risk of amyotrophic lateral sclerosis (ALS), and whether this association is causal remains unknown. We aimed to investigate the potential causal relation between essential nutrients (essential amino acids, essential fatty acids, essential minerals, and essential vitamins) and the risk of ALS using Mendelian randomization (MR) analysis. Large-scale European-based genome-wide association studies’ (GWASs) summary data related to ALS (assembling 27,205 ALS patients and 110,881 controls) and essential nutrient concentrations were separately obtained. MR analysis was performed using the inverse variance–weighted (IVW) method, and sensitivity analysis was conducted by the weighted median method, simple median method, MR–Egger method and MR–PRESSO method. We found a causal association between genetically predicted linoleic acid (LA) and the risk of ALS (OR: 1.066; 95% CI: 1.011–1.125; p = 0.019). An inverse association with ALS risk was noted for vitamin D (OR: 0.899; 95% CI: 0.819–0.987; p = 0.025) and for vitamin E (OR: 0.461; 95% CI: 0.340–0.626; p = 6.25 × 10−7). The sensitivity analyses illustrated similar trends. No causal effect was observed between essential amino acids and minerals on ALS. Our study profiled the effects of diet-derived circulating nutrients on the risk of ALS and demonstrated that vitamin D and vitamin E are protective against the risk of ALS, and LA is a suggested risk factor for ALS. Full article
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Communication
Genetically Predicted Circulating Copper and Risk of Chronic Kidney Disease: A Mendelian Randomization Study
Nutrients 2022, 14(3), 509; https://doi.org/10.3390/nu14030509 - 25 Jan 2022
Cited by 1 | Viewed by 1119
Abstract
Elevated circulating copper levels have been associated with chronic kidney disease (CKD), kidney damage, and decline in kidney function. Using a two sample Mendelian randomization approach where copper-associated genetic variants were used as instrumental variables, genetically predicted higher circulating copper levels were associated [...] Read more.
Elevated circulating copper levels have been associated with chronic kidney disease (CKD), kidney damage, and decline in kidney function. Using a two sample Mendelian randomization approach where copper-associated genetic variants were used as instrumental variables, genetically predicted higher circulating copper levels were associated with higher CKD prevalence (odds ratio 1.17; 95% confidence interval 1.04, 1.32; p-value = 0.009). There was suggestive evidence that genetically predicted higher copper was associated with a lower estimated glomerular filtration rate and a more rapid kidney damage decline. In conclusion, we observed that elevated circulating copper levels may be a causal risk factor for CKD. Full article
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Article
The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study
Nutrients 2022, 14(2), 233; https://doi.org/10.3390/nu14020233 - 06 Jan 2022
Cited by 7 | Viewed by 1549
Abstract
Background & Aims: Previous results from observational, interventional studies and in vitro experiments suggest that certain micronutrients possess anti-viral and immunomodulatory activities. In particular, it has been hypothesized that zinc, selenium, copper and vitamin K1 have strong potential for prophylaxis and [...] Read more.
Background & Aims: Previous results from observational, interventional studies and in vitro experiments suggest that certain micronutrients possess anti-viral and immunomodulatory activities. In particular, it has been hypothesized that zinc, selenium, copper and vitamin K1 have strong potential for prophylaxis and treatment of COVID-19. We aimed to test whether genetically predicted Zn, Se, Cu or vitamin K1 levels have a causal effect on COVID-19 related outcomes, including risk of infection, hospitalization and critical illness. Methods: We employed a two-sample Mendelian Randomization (MR) analysis. Our genetic variants derived from European-ancestry GWAS reflected circulating levels of Zn, Cu, Se in red blood cells as well as Se and vitamin K1 in serum/plasma. For the COVID-19 outcome GWAS, we used infection, hospitalization or critical illness. Our inverse-variance weighted (IVW) MR analysis was complemented by sensitivity analyses including a more liberal selection of variants at a genome-wide sub-significant threshold, MR-Egger and weighted median/mode tests. Results: Circulating micronutrient levels show limited evidence of association with COVID-19 infection, with the odds ratio [OR] ranging from 0.97 (95% CI: 0.87–1.08, p-value = 0.55) for zinc to 1.07 (95% CI: 1.00–1.14, p-value = 0.06)—i.e., no beneficial effect for copper was observed per 1 SD increase in exposure. Similarly minimal evidence was obtained for the hospitalization and critical illness outcomes with OR from 0.98 (95% CI: 0.87–1.09, p-value = 0.66) for vitamin K1 to 1.07 (95% CI: 0.88–1.29, p-value = 0.49) for copper, and from 0.93 (95% CI: 0.72–1.19, p-value = 0.55) for vitamin K1 to 1.21 (95% CI: 0.79–1.86, p-value = 0.39) for zinc, respectively. Conclusions: This study does not provide evidence that supplementation with zinc, selenium, copper or vitamin K1 can prevent SARS-CoV-2 infection, critical illness or hospitalization for COVID-19. Full article
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Article
Genetically Predicted Milk Intake and Risk of Neurodegenerative Diseases
Nutrients 2021, 13(8), 2893; https://doi.org/10.3390/nu13082893 - 23 Aug 2021
Cited by 2 | Viewed by 1719
Abstract
Milk intake has been associated with risk of neurodegenerative diseases in observational studies. Nevertheless, whether the association is causal remains unknown. We adopted Mendelian randomization design to evaluate the potential causal association between milk intake and common neurodegenerative diseases, including multiple sclerosis (MS), [...] Read more.
Milk intake has been associated with risk of neurodegenerative diseases in observational studies. Nevertheless, whether the association is causal remains unknown. We adopted Mendelian randomization design to evaluate the potential causal association between milk intake and common neurodegenerative diseases, including multiple sclerosis (MS), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD). Genetic associations for neurodegenerative diseases were obtained from the International Multiple Sclerosis Genetics Consortium (n = 80,094), FinnGen consortium (n = 176,899), AD GWAS (n = 63,926), Web-Based Study of Parkinson’s Disease (n = 308,518), PDGene (n = 108,990), and ALS GWAS (n = 80,610). Lactase persistence variant rs4988235 (LCT-13910 C > T) was used as the instrumental variable for milk intake. Genetically predicted higher milk intake was associated with a decreased risk of MS and AD and with an increased risk of PD. For each additional milk intake increasing allele, the odds ratios were 0.94 (95% confidence intervals [CI]: 0.91–0.97; p = 1.51 × 10−4) for MS, 0.97 (0.94–0.99; p = 0.019) for AD and 1.09 (95%CI: 1.06–1.12, p = 9.30 × 10−9) for PD. Genetically predicted milk intake was not associated with ALS (odds ratio: 0.97, 95%CI: 0.94–1.01, p = 0.135). Our results suggest that genetically predicted milk intake is associated with a decreased risk of MS and AD but with an increased risk of PD. Further investigations are needed to clarify the underlying mechanisms. Full article
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Reply
Reply to Janssen et al. Comment on “Sobczyk, M.K.; Gaunt, T.R. The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study. Nutrients 2022, 14, 233”
Nutrients 2022, 14(5), 1113; https://doi.org/10.3390/nu14051113 - 07 Mar 2022
Cited by 3 | Viewed by 599
Abstract
In their correspondence arising from our recent manuscript [...] Full article
Comment
Comment on Sobczyk, M.K.; Gaunt, T.R. The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study. Nutrients 2022, 14, 233
Nutrients 2022, 14(5), 1112; https://doi.org/10.3390/nu14051112 - 07 Mar 2022
Cited by 3 | Viewed by 637
Abstract
Sobczyk and Gaunt genetically predicted circulating zinc, selenium, copper, and vitamin K1 levels—instead of directly measuring nutrients in blood—and hypothesized that these levels would associate with SARS-CoV-2 infection and COVID-19 severity [...] Full article
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