Editorial

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2 pages, 174 KiB

Open AccessEditorial

Mendelian Randomization Studies on Nutritional Factors and Health Outcomes

by Susanna C. Larsson

Nutrients 2022, 14(14), 2780; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14142780 - 06 Jul 2022

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Abstract

Poor diet is a leading cause of morbidity and mortality [...] Full article

(This article belongs to the Special Issue Mendelian Randomization Studies on Nutritional Factors and Health Outcomes)

Research

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5 pages, 1065 KiB

Open AccessCommunication

Plasma Caffeine Levels and Risk of Alzheimer’s Disease and Parkinson’s Disease: Mendelian Randomization Study

by Susanna C. Larsson, Benjamin Woolf and Dipender Gill

Nutrients 2022, 14(9), 1697; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14091697 - 19 Apr 2022

Cited by 18 | Viewed by 6767

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

(This article belongs to the Special Issue Mendelian Randomization Studies on Nutritional Factors and Health Outcomes)

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6 pages, 855 KiB

Open AccessArticle

Alcohol, Coffee, and Milk Intake in Relation to Epilepsy Risk

by Zhizhong Zhang, Mengmeng Wang, Shuai Yuan and Xinfeng Liu

Nutrients 2022, 14(6), 1153; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14061153 - 09 Mar 2022

Cited by 5 | Viewed by 6523

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

(This article belongs to the Special Issue Mendelian Randomization Studies on Nutritional Factors and Health Outcomes)

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16 pages, 1959 KiB

Open AccessArticle

Dietary-Derived Essential Nutrients and Amyotrophic Lateral Sclerosis: A Two-Sample Mendelian Randomization Study

by Kailin Xia, Yajun Wang, Linjing Zhang, Lu Tang, Gan Zhang, Tao Huang, Ninghao Huang and Dongsheng Fan

Nutrients 2022, 14(5), 920; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14050920 - 22 Feb 2022

Cited by 11 | Viewed by 4052

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

(This article belongs to the Special Issue Mendelian Randomization Studies on Nutritional Factors and Health Outcomes)

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5 pages, 373 KiB

Open AccessCommunication

Genetically Predicted Circulating Copper and Risk of Chronic Kidney Disease: A Mendelian Randomization Study

by Shafqat Ahmad, Johan Ärnlöv and Susanna C. Larsson

Nutrients 2022, 14(3), 509; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14030509 - 25 Jan 2022

Cited by 11 | Viewed by 3213

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

(This article belongs to the Special Issue Mendelian Randomization Studies on Nutritional Factors and Health Outcomes)

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17 pages, 6538 KiB

Open AccessEditor’s ChoiceArticle

The Effect of Circulating Zinc, Selenium, Copper and Vitamin K₁ on COVID-19 Outcomes: A Mendelian Randomization Study

by Maria K. Sobczyk and Tom R. Gaunt

Nutrients 2022, 14(2), 233; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14020233 - 06 Jan 2022

Cited by 24 | Viewed by 5151

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

(This article belongs to the Special Issue Mendelian Randomization Studies on Nutritional Factors and Health Outcomes)

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7 pages, 1054 KiB

Open AccessArticle

Genetically Predicted Milk Intake and Risk of Neurodegenerative Diseases

by Zhizhong Zhang, Mengmeng Wang, Shuai Yuan, Susanna C. Larsson and Xinfeng Liu

Nutrients 2021, 13(8), 2893; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13082893 - 23 Aug 2021

Cited by 6 | Viewed by 4504

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

(This article belongs to the Special Issue Mendelian Randomization Studies on Nutritional Factors and Health Outcomes)

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2 pages, 185 KiB

Open AccessReply

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”

by Maria K. Sobczyk and Tom R. Gaunt

Nutrients 2022, 14(5), 1113; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14051113 - 07 Mar 2022

Cited by 4 | Viewed by 1923

Abstract

In their correspondence arising from our recent manuscript [...] Full article

(This article belongs to the Special Issue Mendelian Randomization Studies on Nutritional Factors and Health Outcomes)

2 pages, 180 KiB

Open AccessComment

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

by Rob Janssen, Cees Vermeer, Jona Walk and Allan Linneberg

Nutrients 2022, 14(5), 1112; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14051112 - 07 Mar 2022

Cited by 3 | Viewed by 1937

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

(This article belongs to the Special Issue Mendelian Randomization Studies on Nutritional Factors and Health Outcomes)

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