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https://www.readbyqxmd.com/read/28645180/alcohol-metabolism-and-oesophageal-cancer-a-systematic-review-of-the-evidence
#1
Marco Matejcic, M J Gunter, Pietro Ferrari
Alcohol is a major risk factor for oesophageal squamous cell carcinoma (OSCC), the most prevalent histological subtype of oesophageal cancer (OC) worldwide. The metabolism of alcohol is regulated by specific enzymes whose activity and expression is influenced by genetic polymorphisms. We conducted a systematic review of current epidemiological evidence of the relationship between alcohol intake and OC risk, including the role of tobacco smoking and functional polymorphisms of dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs)...
June 22, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28639078/a-genome-wide-expression-association-analysis-identifies-genes-and-pathways-associated-with-amyotrophic-lateral-sclerosis
#2
Yanan Du, Yan Wen, Xiong Guo, Jingcan Hao, Wenyu Wang, Awen He, Qianrui Fan, Ping Li, Li Liu, Xiao Liang, Feng Zhang
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with strong genetic components. To identity novel risk variants for ALS, utilizing the latest genome-wide association studies (GWAS) and eQTL study data, we conducted a genome-wide expression association analysis by summary data-based Mendelian randomization (SMR) method. Summary data were derived from a large-scale GWAS of ALS, involving 12577 cases and 23475 controls. The eQTL annotation dataset included 923,021 cis-eQTL for 14,329 genes and 4732 trans-eQTL for 2612 genes...
June 21, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28635950/genetically-predicted-high-body-mass-index-was-associated-with-increased-gastric-cancer-risk
#3
Yingying Mao, Caiwang Yan, Qun Lu, Meng Zhu, Fei Yu, Cheng Wang, Juncheng Dai, Hongxia Ma, Zhibin Hu, Hongbing Shen, Guangfu Jin
Epidemiological studies have linked body mass index (BMI) with risk of gastrointestinal cancers. However, for gastric cancer, the relationship is more controversial. In particular, it is unclear whether the observed association is due to confounding or bias inherent in conventional observational studies. To investigate whether BMI is causally associated with gastric cancer risk, we applied Mendelian randomization using individual-level data from 2631 gastric cancer cases and 4373 cancer-free controls. We derived a weighted genetic risk score (wGRS) using 37 BMI-associated genetic variants as an instrumental variable...
June 21, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28632283/the-impact-of-whole-genome-sequencing-on-the-primary-care-and-outcomes-of-healthy-adult-patients-a-pilot-randomized-trial
#4
Jason L Vassy, Kurt D Christensen, Erica F Schonman, Carrie L Blout, Jill O Robinson, Joel B Krier, Pamela M Diamond, Matthew Lebo, Kalotina Machini, Danielle R Azzariti, Dmitry Dukhovny, David W Bates, Calum A MacRae, Michael F Murray, Heidi L Rehm, Amy L McGuire, Robert C Green
Background: Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value. Objective: To describe the effect on clinical care and outcomes of adding WGS to standardized family history assessment in primary care. Design: Pilot randomized trial. (ClinicalTrials.gov: NCT01736566). Setting: Academic primary care practices. Participants: 9 primary care physicians (PCPs) and 100 generally healthy patients recruited at ages 40 to 65 years...
June 27, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28627485/limitations-of-vitamin-d-supplementation-trials-why-observational-studies-will-continue-to-help-determine-the-role-of-vitamin-d-in-health
#5
REVIEW
Robert Scragg
Observational studies have shown that low vitamin D status is associated with an increased risk of a wide range of diseases. The body of observational evidence now is so large, that there have been many calls for randomized controlled trials (RCT) of vitamin D supplementation to confirm once and for all whether increasing body vitamin D levels prevents these diseases. These calls have arisen because of concern that confounding and reverse causation may explain many of the results from observational studies...
June 13, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28624884/age-at-menarche-and-lung-function-a-mendelian-randomization-study
#6
Dipender Gill, Nuala A Sheehan, Matthias Wielscher, Nick Shrine, Andre F S Amaral, John R Thompson, Raquel Granell, Bénédicte Leynaert, Francisco Gómez Real, Ian P Hall, Martin D Tobin, Juha Auvinen, Susan M Ring, Marjo-Riitta Jarvelin, Louise V Wain, John Henderson, Deborah Jarvis, Cosetta Minelli
A trend towards earlier menarche in women has been associated with childhood factors (e.g. obesity) and hypothesised environmental exposures (e.g. endocrine disruptors present in household products). Observational evidence has shown detrimental effects of early menarche on various health outcomes including adult lung function, but these might represent spurious associations due to confounding. To address this we used Mendelian randomization where genetic variants are used as proxies for age at menarche, since genetic associations are not affected by classical confounding...
June 17, 2017: European Journal of Epidemiology
https://www.readbyqxmd.com/read/28619195/association-of-triglyceride-related-genetic-variants-with-mitral%C3%A2-annular%C3%A2-calcification
#7
Mehdi Afshar, Kevin Luk, Ron Do, Line Dufresne, David S Owens, Tamara B Harris, Gina M Peloso, Kathleen F Kerr, Quenna Wong, Albert V Smith, Mathew J Budoff, Jerome I Rotter, L Adrienne Cupples, Stephen S Rich, James C Engert, Vilmundur Gudnason, Christopher J O'Donnell, Wendy S Post, George Thanassoulis
BACKGROUND: Mitral annular calcium (MAC), commonly identified by cardiac imaging, is associated with cardiovascular events and predisposes to the development of clinically important mitral valve regurgitation and mitral valve stenosis. However, its biological determinants remain largely unknown. OBJECTIVES: The authors sought to evaluate whether a genetic predisposition to elevations in plasma lipids is associated with the presence of MAC. METHODS: The authors used 3 separate Mendelian randomization techniques to evaluate the associations of lipid genetic risk scores (GRS) with MAC in 3 large patient cohorts: the Framingham Health Study, MESA (Multiethnic European Study of Atherosclerosis), and the AGE-RS (Age, Gene/Environment Susceptibility-Reykjavik Study)...
June 20, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28609829/body-mass-index-and-risk-of-alzheimer-disease-a-mendelian-randomization-study-of-399-536-individuals
#8
Liv Tybjærg Nordestgaard, Anne Tybjærg-Hansen, Børge G. Nordestgaard, Ruth Frikke-Schmidt
Context: Recently, data on two million people established that low body mass index (BMI) is associated with increased risk of dementia. Whether this observational association reflects a causal effect remains to be clarified. Objective: We tested the hypothesis that there is a causal association between low BMI and high risk of Alzheimer disease. Design, Setting and Participants: Using a Mendelian randomization approach, we studied 95,578 individuals from the Copenhagen General Population Study (CGPS) with up to 36 years of follow-up, and consortia data on 303,958 individuals from the Genetic Investigation of Anthropometric Traits (GIANT) and the International Genomics of Alzheimer's Project (IGAP)...
May 9, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28601624/age-at-menarche-and-cardiovascular-risk-factors-using-mendelian-randomization-in-the-guangzhou-biobank-cohort-study
#9
Shiu Lun Au Yeung, Chaoqiang Jiang, Kar Keung Cheng, Lin Xu, Weisen Zhang, Tai Hing Lam, Gabriel Matthew Leung, C Mary Schooling
Observational studies show earlier age at menarche associated with higher risk of cardiovascular disease although these studies could be confounded by childhood obesity or childhood socioeconomic position. We tested the hypothesis that earlier age at menarche is associated with poorer cardiovascular risk factors using a Mendelian randomization design. We conducted a Mendelian randomization study in a large Southern Chinese cohort, the Guangzhou Biobank Cohort Study (n=12,279), to clarify the causal role of menarche in cardiovascular disease risk factors including blood pressure, lipids, fasting glucose, adiposity and type 2 diabetes...
June 8, 2017: Preventive Medicine
https://www.readbyqxmd.com/read/28594918/obesity-metabolic-factors-and-risk-of-different-histological-types-of-lung-cancer-a-mendelian-randomization-study
#10
Robert Carreras-Torres, Mattias Johansson, Philip C Haycock, Kaitlin H Wade, Caroline L Relton, Richard M Martin, George Davey Smith, Demetrius Albanes, Melinda C Aldrich, Angeline Andrew, Susanne M Arnold, Heike Bickeböller, Stig E Bojesen, Hans Brunnström, Jonas Manjer, Irene Brüske, Neil E Caporaso, Chu Chen, David C Christiani, W Jay Christian, Jennifer A Doherty, Eric J Duell, John K Field, Michael P A Davies, Michael W Marcus, Gary E Goodman, Kjell Grankvist, Aage Haugen, Yun-Chul Hong, Lambertus A Kiemeney, Erik H F M van der Heijden, Peter Kraft, Mikael B Johansson, Stephen Lam, Maria Teresa Landi, Philip Lazarus, Loïc Le Marchand, Geoffrey Liu, Olle Melander, Sungshim L Park, Gad Rennert, Angela Risch, Eric B Haura, Ghislaine Scelo, David Zaridze, Anush Mukeriya, Milan Savić, Jolanta Lissowska, Beata Swiatkowska, Vladimir Janout, Ivana Holcatova, Dana Mates, Matthew B Schabath, Hongbing Shen, Adonina Tardon, M Dawn Teare, Penella Woll, Ming-Sound Tsao, Xifeng Wu, Jian-Min Yuan, Rayjean J Hung, Christopher I Amos, James McKay, Paul Brennan
BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls...
2017: PloS One
https://www.readbyqxmd.com/read/28594127/no-clear-support-for-a-role-for-vitamin-d-in-parkinson-s-disease-a-mendelian-randomization-study
#11
Susanna C Larsson, Andrew B Singleton, Mike A Nalls, J Brent Richards
BACKGROUND: Observational studies have found that relative to healthy controls, patients with Parkinson's disease have lower circulating concentrations of 25-hydroxyvitamin D, a clinical biomarker of vitamin D status. However, the causality of this association is uncertain. We undertook a Mendelian randomization study to investigate whether genetically decreased 25-hydroxyvitamin D concentrations are associated with PD to minimize confounding and prevent bias because of reverse causation...
June 8, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28590373/nature-as-a-trialist-deconstructing-the-analogy-between-mendelian-randomization-and-randomized-trials
#12
Sonja A Swanson, Henning Tiemeier, M Arfan Ikram, Miguel A Hernán
Mendelian randomization (MR) studies are often described as naturally occurring randomized trials in which genetic factors are randomly assigned by nature. Conceptualizing MR studies as randomized trials has profound implications for their design, conduct, reporting, and interpretation. For example, analytic practices that are discouraged in randomized trials should also be discouraged in MR studies.Here, we deconstruct the oft-made analogy between MR and randomized trials. We describe four key threats to the analogy between MR studies and randomized trials: (1) exchangeability is not guaranteed; (2) time zero (and therefore the time for setting eligibility criteria) is unclear; (3) the treatment assignment is often measured with error; and (4) adherence is poorly defined...
June 5, 2017: Epidemiology
https://www.readbyqxmd.com/read/28586461/genetically-low-vitamin-d-concentrations-and-myopic-refractive-error-a-mendelian-randomization-study
#13
Gabriel Cuellar-Partida, Katie M Williams, Seyhan Yazar, Jeremy A Guggenheim, Alex W Hewitt, Cathy Williams, Jie Jin Wang, Pik-Fang Kho, Seang Mei Saw, Ching-Yu Cheng, Tien Yin Wong, Tin Aung, Terri L Young, J Willem L Tideman, Jost B Jonas, Paul Mitchell, Robert Wojciechowski, Dwight Stambolian, Pirro Hysi, Christopher J Hammond, David A Mackey, Robyn M Lucas, Stuart MacGregor
Background: Myopia prevalence has increased in the past 20 years, with many studies linking the increase to reduced time spent outdoors. A number of recent observational studies have shown an inverse association between vitamin D [25(OH)D] serum levels and myopia. However, in such studies it is difficult to separate the effects of time outdoors and vitamin D levels. In this work we use Mendelian randomization (MR) to assess if genetically determined 25(OH)D levels contribute to the degree of myopia...
June 6, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28575313/power-calculator-for-instrumental-variable-analysis-in-pharmacoepidemiology
#14
Venexia M Walker, Neil M Davies, Frank Windmeijer, Stephen Burgess, Richard M Martin
Background: Instrumental variable analysis, for example with physicians' prescribing preferences as an instrument for medications issued in primary care, is an increasingly popular method in the field of pharmacoepidemiology. Existing power calculators for studies using instrumental variable analysis, such as Mendelian randomization power calculators, do not allow for the structure of research questions in this field. This is because the analysis in pharmacoepidemiology will typically have stronger instruments and detect larger causal effects than in other fields...
May 30, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28572633/cognitive-ability-and-physical-health-a-mendelian-randomization-study
#15
Saskia P Hagenaars, Catharine R Gale, Ian J Deary, Sarah E Harris
Causes of the association between cognitive ability and health remain unknown, but may reflect a shared genetic aetiology. This study examines the causal genetic associations between cognitive ability and physical health. We carried out two-sample Mendelian randomization analyses using the inverse-variance weighted method to test for causality between later life cognitive ability, educational attainment (as a proxy for cognitive ability in youth), BMI, height, systolic blood pressure, coronary artery disease, and type 2 diabetes using data from six independent GWAS consortia and the UK Biobank sample (N = 112 151)...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28569269/mendelian-randomization-in-cardiometabolic-disease-challenges-in-evaluating-causality
#16
REVIEW
Michael V Holmes, Mika Ala-Korpela, George Davey Smith
Mendelian randomization (MR) is a burgeoning field that involves the use of genetic variants to assess causal relationships between exposures and outcomes. MR studies can be straightforward; for example, genetic variants within or near the encoding locus that is associated with protein concentrations can help to assess their causal role in disease. However, a more complex relationship between the genetic variants and an exposure can make findings from MR more difficult to interpret. In this Review, we describe some of these challenges in interpreting MR analyses, including those from studies using genetic variants to assess causality of multiple traits (such as branched-chain amino acids and risk of diabetes mellitus); studies describing pleiotropic variants (for example, C-reactive protein and its contribution to coronary heart disease); and those investigating variants that disrupt normal function of an exposure (for example, HDL cholesterol or IL-6 and coronary heart disease)...
June 1, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28564679/difficulties-in-testing-the-instrument-strength-independent-of-direct-effect-assumption-in-mendelian-randomization
#17
Jack Bowden, Stephen Burgess, George Davey Smith
No abstract text is available yet for this article.
May 31, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28556459/does-coffee-consumption-impact-on-heaviness-of-smoking
#18
Jennifer J Ware, Julie-Anne Tanner, Amy E Taylor, Zhao Bin, Philip Haycock, Jack Bowden, Peter J Rogers, George Davey Smith, Rachel F Tyndale, Marcus R Munafo
BACKGROUND AND AIMS: Coffee consumption and cigarette smoking are strongly associated, but whether this association is causal remains unclear. We sought to: 1) determine whether coffee consumption causally influences cigarette smoking, 2) estimate the magnitude of any association, and 3) explore potential mechanisms. DESIGN: We used Mendelian randomization (MR) analyses of observational data, using publicly available summarised data from the Tobacco and Genetics (TAG) consortium, individual level data from the UK Biobank, and in vitro experiments of candidate compounds...
May 27, 2017: Addiction
https://www.readbyqxmd.com/read/28552732/integrating-genome-wide-association-study-and-expression-quantitative-trait-loci-data-identifies-multiple-genes-and-gene-set-associated-with-neuroticism
#19
Qianrui Fan, Wenyu Wang, Jingcan Hao, Awen He, Yan Wen, Xiong Guo, Cuiyan Wu, Yujie Ning, Xi Wang, Sen Wang, Feng Zhang
Neuroticism is a fundamental personality trait with significant genetic determinant. To identify novel susceptibility genes for neuroticism, we conducted an integrative analysis of genomic and transcriptomic data of genome wide association study (GWAS) and expression quantitative trait locus (eQTL) study. GWAS summary data was driven from published studies of neuroticism, totally involving 170,906 subjects. eQTL dataset containing 927,753 eQTLs were obtained from an eQTL meta-analysis of 5311 samples. Integrative analysis of GWAS and eQTL data was conducted by summary data-based Mendelian randomization (SMR) analysis software...
May 25, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28552197/large-scale-identification-of-common-trait-and-disease-variants-affecting-gene-expression
#20
Mads Engel Hauberg, Wen Zhang, Claudia Giambartolomei, Oscar Franzén, David L Morris, Timothy J Vyse, Arno Ruusalepp, Pamela Sklar, Eric E Schadt, Johan L M Björkegren, Panos Roussos
Genome-wide association studies (GWASs) have identified a multitude of genetic loci involved with traits and diseases. However, it is often unclear which genes are affected in such loci and whether the associated genetic variants lead to increased or decreased gene function. To mitigate this, we integrated associations of common genetic variants in 57 GWASs with 24 studies of expression quantitative trait loci (eQTLs) from a broad range of tissues by using a Mendelian randomization approach. We discovered a total of 3,484 instances of gene-trait-associated changes in expression at a false-discovery rate < 0...
June 1, 2017: American Journal of Human Genetics
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