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Mendelian Randomization Nutrition

Wen-Wen Cheng, Qiang Zhu, Hong-Yu Zhang
We applied Mendelian randomization analyses to investigate the potential causality between blood minerals (calcium, magnesium, iron, copper, and zinc) and osteoporosis (OP), gout, rheumatoid arthritis (RA), type 2 diabetes (T2D), Alzheimer's disease (AD), bipolar disorder (BD), schizophrenia , Parkinson's disease and major depressive disorder. Single nucleotide polymorphisms (SNPs) that are independent ( r ² < 0.01) and are strongly related to minerals ( p < 5 × 10-8 ) are selected as instrumental variables...
February 12, 2019: Nutrients
Sabine R Zwakenberg, Sharon Remmelzwaal, Joline W J Beulens, Sarah L Booth, Stephen Burgess, Hassan S Dashti, Fumiaki Imamura, Edith J M Feskens, Yvonne T van der Schouw, Ivonne Sluijs
This study aims to investigate the causal relation between circulating phylloquinone (vitamin K1) concentrations and type 2 diabetes using a Mendelian Randomization (MR) approach. We used data from thee cohorts: the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, Diabetes Genetics Replication and Meta-analysis (DIAGRAM) and the UK Biobank, resulting in 69,647 type 2 diabetes cases. We calculated a weighted genetic risk score including four genetic variants previously found to be associated with circulating phylloquinone concentrations...
October 23, 2018: Diabetes
John F Trepanowski, John P A Ioannidis
A large majority of human nutrition research uses nonrandomized observational designs, but this has led to little reliable progress. This is mostly due to many epistemologic problems, the most important of which are as follows: difficulty detecting small (or even tiny) effect sizes reliably for nutritional risk factors and nutrition-related interventions; difficulty properly accounting for massive confounding among many nutrients, clinical outcomes, and other variables; difficulty measuring diet accurately; and suboptimal research reporting...
July 1, 2018: Advances in Nutrition
Stephen Burgess, Brian A Ference, James R Staley, Daniel F Freitag, Amy M Mason, Sune F Nielsen, Peter Willeit, Robin Young, Praveen Surendran, Savita Karthikeyan, Thomas R Bolton, James E Peters, Pia R Kamstrup, Anne Tybjærg-Hansen, Marianne Benn, Anne Langsted, Peter Schnohr, Signe Vedel-Krogh, Camilla J Kobylecki, Ian Ford, Chris Packard, Stella Trompet, J Wouter Jukema, Naveed Sattar, Emanuele Di Angelantonio, Danish Saleheen, Joanna M M Howson, Børge G Nordestgaard, Adam S Butterworth, John Danesh
Importance: Human genetic studies have indicated that plasma lipoprotein(a) (Lp[a]) is causally associated with the risk of coronary heart disease (CHD), but randomized trials of several therapies that reduce Lp(a) levels by 25% to 35% have not provided any evidence that lowering Lp(a) level reduces CHD risk. Objective: To estimate the magnitude of the change in plasma Lp(a) levels needed to have the same evidence of an association with CHD risk as a 38.67-mg/dL (ie, 1-mmol/L) change in low-density lipoprotein cholesterol (LDL-C) level, a change that has been shown to produce a clinically meaningful reduction in the risk of CHD...
July 1, 2018: JAMA Cardiology
Stephen L Pinkosky, Pieter H E Groot, Narendra D Lalwani, Gregory R Steinberg
Chronic overnutrition and a sedentary lifestyle promote imbalances in metabolism, often manifesting as risk factors for life-threating diseases such as atherosclerotic cardiovascular disease (ASCVD) and nonalcoholic fatty liver disease (NAFLD). Nucleocytosolic acetyl-coenzyme A (CoA) has emerged as a central signaling node used to coordinate metabolic adaptations in response to a changing nutritional status. ATP-citrate lyase (ACL) is the enzyme primarily responsible for the production of extramitochondrial acetyl-CoA and is thus strategically positioned at the intersection of nutrient catabolism and lipid biosynthesis...
November 2017: Trends in Molecular Medicine
Wolfgang Göpel, Josephine Drese, Tanja K Rausch, Nele Twisselmann, Bettina Bohnhorst, Andreas Müller, Axel Franz, Andreas Ziegler, Christoph Härtel, Egbert Herting
BackgroundIntestinal iron is a nutritional compound, which is essential for enteric microbiota. We evaluated the hypothesis that polymorphisms, which are known modifiers of intestinal iron uptake in adults, are associated with necrotizing enterocolitis (NEC) in preterm infants.MethodsPreterm infants (birth weight below 1,500 g) were studied. Single-nucleotide polymorphisms with known effects on serum iron levels (rs1800562, rs1799945, and rs855791) were determined using PCR. The effects of polymorphisms on NEC surgery were tested by Mendelian randomization...
January 2018: Pediatric Research
L T Møllehave, T Skaaby, K S Simonsen, B H Thuesen, E L Mortensen, C H Sandholt, O Pedersen, N Grarup, T Hansen, A Linneberg
BACKGROUND/OBJECTIVES: Observational studies have suggested low serum levels of vitamin B12 or folate to be risk factors of depression and anxiety. However, these results may be biased by confounding and reverse causation. Mendelian randomization studies are not subject to these limitations. The aim was to examine the association of genetic scores of vitamin B12 and folate-associated alleles with depression and anxiety. SUBJECTS/METHODS: The study included 4126 participants from two Danish population-based studies...
September 2017: European Journal of Clinical Nutrition
Katharina Nimptsch, Mingyang Song, Krasimira Aleksandrova, Michail Katsoulis, Heinz Freisling, Mazda Jenab, Marc J Gunter, Konstantinos K Tsilidis, Elisabete Weiderpass, H Bas Bueno-De-Mesquita, Dawn Q Chong, Majken K Jensen, Chunsen Wu, Kim Overvad, Tilman Kühn, Myrto Barrdahl, Olle Melander, Karin Jirström, Petra H Peeters, Sabina Sieri, Salvatore Panico, Amanda J Cross, Elio Riboli, Bethany Van Guelpen, Robin Myte, José María Huerta, Miguel Rodriguez-Barranco, José Ramón Quirós, Miren Dorronsoro, Anne Tjønneland, Anja Olsen, Ruth Travis, Marie-Christine Boutron-Ruault, Franck Carbonnel, Gianluca Severi, Catalina Bonet, Domenico Palli, Jürgen Janke, Young-Ae Lee, Heiner Boeing, Edward L Giovannucci, Shuji Ogino, Charles S Fuchs, Eric Rimm, Kana Wu, Andrew T Chan, Tobias Pischon
Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene...
May 2017: European Journal of Epidemiology
Q Yang, S L Lin, S L Au Yeung, M K Kwok, L Xu, G M Leung, C M Schooling
BACKGROUND/OBJECTIVES: Milk provides protein and micronutrients, and is recommended by some dietary guidelines, particularly for bone health. Meta-analysis of small randomized controlled trials suggests that milk may increase bone mineral density, but they are very heterogeneous. No randomized controlled trial has assessed the effects of milk on major chronic diseases. Previous Mendelian randomization studies of milk did not consider bone health, found no effects on ischemic heart disease (IHD) or type 2 diabetes (T2D) but higher body mass index...
August 2017: European Journal of Clinical Nutrition
J V Zhao, C M Schooling
BACKGROUND/OBJECTIVES: Observationally, homocysteine is positively associated with ischemic heart disease (IHD) and unhealthy lipids; folate and vitamin B12, which reduce homocysteine, are associated with lower IHD risk and healthy lipids. Randomized controlled trials have shown no benefits of folate and vitamin B12 for IHD. To clarify the role of these potential targets of intervention in IHD we assessed how genetically determined homocysteine, folate and vitamin-B12-affected IHD and lipids...
February 2017: European Journal of Clinical Nutrition
Ivonne Sluijs, Michael V Holmes, Yvonne T van der Schouw, Joline W J Beulens, Folkert W Asselbergs, José María Huerta, Tom M Palmer, Larraitz Arriola, Beverley Balkau, Aurelio Barricarte, Heiner Boeing, Françoise Clavel-Chapelon, Guy Fagherazzi, Paul W Franks, Diana Gavrila, Rudolf Kaaks, Kay Tee Khaw, Tilman Kühn, Esther Molina-Montes, Lotte Maxild Mortensen, Peter M Nilsson, Kim Overvad, Domenico Palli, Salvatore Panico, J Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, Núria Sala, Julie A Schmidt, Robert A Scott, Sabina Sieri, Nadia Slimani, Annemieke M W Spijkerman, Anne Tjonneland, Ruth C Travis, Rosario Tumino, Daphne L van der A, Stephen J Sharp, Nita G Forouhi, Claudia Langenberg, Elio Riboli, Nicholas J Wareham
We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid-associated loci. We used data of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries. During a mean (SD) follow-up of 10 (4) years, 10,576 verified incident case subjects with type 2 diabetes were ascertained...
August 2015: Diabetes
Katharina Nimptsch, Krasimira Aleksandrova, Heiner Boeing, Jürgen Janke, Young-Ae Lee, Mazda Jenab, So Yeon Kong, Konstantinos K Tsilidis, Elisabete Weiderpass, H B As Bueno-De-Mesquita, Peter D Siersema, Eugène H J M Jansen, Antonia Trichopoulou, Anne Tjønneland, Anja Olsen, Chunsen Wu, Kim Overvad, Marie-Christine Boutron-Ruault, Antoine Racine, Heinz Freisling, Verena Katzke, Rudolf Kaaks, Pagona Lagiou, Dimitrios Trichopoulos, Gianluca Severi, Alessio Naccarati, Amalia Mattiello, Domenico Palli, Sara Grioni, Rosario Tumino, Petra H Peeters, Ingrid Ljuslinder, Hanna Nyström, Jenny Brändstedt, María-José Sánchez, Aurelio Barricarte Gurrea, Catalina Bonet Bonet, María-Dolores Chirlaque, Miren Dorronsoro, José Ramón Quirós, Ruth C Travis, Kay-Tee Khaw, Nick Wareham, Elio Riboli, Marc J Gunter, Tobias Pischon
Fetuin-A, also referred to as α2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls...
August 15, 2015: International Journal of Cancer. Journal International du Cancer
Chittaranjan S Yajnik, Giriraj R Chandak, Charudatta Joglekar, Prachi Katre, Dattatray S Bhat, Suraj N Singh, Charles S Janipalli, Helga Refsum, Ghattu Krishnaveni, Sargoor Veena, Clive Osmond, Caroline H D Fall
BACKGROUND: Disturbed one-carbon (1-C) metabolism in the mother is associated with poor fetal growth but causality of this relationship has not been established. METHODS: We studied the association between maternal total homocysteine and offspring birthweight in the Pune Maternal Nutrition Study (PMNS, Pune, India) and Parthenon Cohort Study (Mysore, India). We tested for evidence of causality within a Mendelian randomization framework, using a methylenetetrahydrofolatereductase (MTHFR) gene variant rs1801133 (earlier known as 677C→T) by instrumental variable and triangulation analysis, separately and using meta-analysis...
October 2014: International Journal of Epidemiology
Katharina Nimptsch, Krasimira Aleksandrova, Heiner Boeing, Jürgen Janke, Young-Ae Lee, Mazda Jenab, H Bas Bueno-de-Mesquita, Eugène H J M Jansen, Konstantinos K Tsilidis, Antonia Trichopoulou, Elisabete Weiderpass, Chunsen Wu, Kim Overvad, Anne Tjønneland, Marie-Christine Boutron-Ruault, Laure Dossus, Antoine Racine, Rudolf Kaaks, Federico Canzian, Pagona Lagiou, Dimitrios Trichopoulos, Domenico Palli, Claudia Agnoli, Rosario Tumino, Paolo Vineis, Salvatore Panico, Anders Johansson, Bethany Van Guelpen, Kay-Tee Khaw, Nick Wareham, Petra H Peeters, J Ramón Quirós, Adoración Venceslá García, Esther Molina-Montes, Miren Dorronsoro, María-Dolores Chirlaque, Aurelio Barricarte Gurrea, Timothy J Key, Talita Duarte-Salles, Magdalena Stepien, Marc J Gunter, Elio Riboli, Tobias Pischon
High blood concentrations of C-reactive protein (CRP) have been associated with elevated risk of colorectal cancer in several prospective studies including the European Prospective Investigation into Cancer and Nutrition (EPIC), but it is unknown whether these observations reflect a causal relationship. We aimed to investigate whether CRP genetic variants associated with lifelong higher CRP concentrations translate into higher colorectal cancer risk. We conducted a prospective nested case-control study within EPIC including 727 cases diagnosed between 1992 and 2003 and 727 matched controls selected according to an incidence-density sampling protocol...
March 1, 2015: International Journal of Cancer. Journal International du Cancer
S J Lewis, C Bonilla, M-J Brion, D A Lawlor, D Gunnell, Y Ben-Shlomo, A Ness, G D Smith
BACKGROUND/OBJECTIVES: Iron is fundamental to many basic biological functions, and animal studies suggest that iron deficiency early in life can have a lasting impact on the developing brain. SUBJECTS/METHODS: We used a population-based cohort of mothers and their children to assess the effect of iron status among pregnant women on the cognitive ability of their offspring. But to avoid the inherent confounding that occurs within observational epidemiology studies we examined the association of maternal genotype at single-nucleotide polymorphisms in the genes HFE (rs1799945) and (rs1800562), TF (rs3811647) and TMPRSS6 (rs1800562), which are related to iron, haemoglobin or transferrin levels, on their child's cognitive test scores at age 8...
April 2014: European Journal of Clinical Nutrition
Hyunseung Kang, Benno Kreuels, Ohene Adjei, Ralf Krumkamp, Jürgen May, Dylan S Small
BACKGROUND: Previous studies on the association of malaria and stunted growth delivered inconsistent results. These conflicting results may be due to different levels of confounding and to considerable difficulties in elucidating a causal relationship. Randomized experiments are impractical and previous observational studies have not fully controlled for potential confounding including nutritional deficiencies, breastfeeding habits, other infectious diseases and socioeconomic status. METHODS: This study aims to estimate the causal effect between malaria episodes and stunted growth by applying a combination of Mendelian randomization, using the sickle cell trait, and matching...
October 2013: International Journal of Epidemiology
Ricardo Almon, Eva Elisa Álvarez-León, Lluís Serra-Majem
BACKGROUND: European lactose tolerance genotype (LCT -13910 C>T, rs4988234) has been positively associated to body mass indexes (BMI) in a meta-analysis of 31,720 individuals of northern and central European descent. A strong association of lactase persistence (LP) with BMI and obesity has also been traced in a Spanish Mediterranean population. The aim of this study was to analyze a potential association of LP compared to lactase non-persistence (LNP) with BMI in inhabitants of the Canary Islands of Spain using Mendelian randomization...
2012: PloS One
James B Kirkbride, Ezra Susser, Marija Kundakovic, Jacob K Kresovich, George Davey Smith, Caroline L Relton
We posit that maternal prenatal nutrition can influence offspring schizophrenia risk via epigenetic effects. In this article, we consider evidence that prenatal nutrition is linked to epigenetic outcomes in offspring and schizophrenia in offspring, and that schizophrenia is associated with epigenetic changes. We focus upon one-carbon metabolism as a mediator of the pathway between perturbed prenatal nutrition and the subsequent risk of schizophrenia. Although post-mortem human studies demonstrate DNA methylation changes in brains of people with schizophrenia, such studies cannot establish causality...
June 2012: Epigenomics
George Davey Smith
Differences in diet appear to contribute substantially to the burden of disease in populations, and therefore changes in diet could lead to major improvements in public health. This is predicated on the reliable identification of causal effects of nutrition on health, and unfortunately nutritional epidemiology has deficiencies in terms of identifying these. This is reflected in the many cases where observational studies have suggested that a nutritional factor is protective against disease, and randomized controlled trials have failed to verify this...
February 2011: Genes & Nutrition
Lucilla Poston, Lucien F Harthoorn, Eline M Van Der Beek
Obesity among pregnant women is becoming one of the most important women's health issues. Obesity is associated with increased risk of almost all pregnancy complications: gestational hypertension, preeclampsia, gestational diabetes mellitus, delivery of large-for-GA infants, and higher incidence of congenital defects all occur more frequently than in women with a normal BMI. Evidence shows that a child of an obese mother may suffer from exposure to a suboptimal in utero environment and that early life adversities may extend into adulthood...
February 2011: Pediatric Research
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