mendelian randomization analysis


Summary: The use of the GENETIC VARIATION of known functions or phenotypes to correlate the causal effects of those functions or phenotypes with a disease outcome.

Top Publications

  1. Manousaki D, Paternoster L, Standl M, Moffatt M, Farrall M, Bouzigon E, et al. Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study. PLoS Med. 2017;14:e1002294 pubmed publisher
  2. May Wilson S, Sud A, Law P, Palin K, Tuupanen S, Gylfe A, et al. Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis. Eur J Cancer. 2017;84:228-238 pubmed publisher
    ..17, 95% CI: 1.01-1.35, P = 0.041). Results from our analysis are broadly consistent with a pro-inflammatory FA profile having a detrimental effect in terms of CRC risk. ..
  3. Larsson S, Burgess S, Michaelsson K. Association of Genetic Variants Related to Serum Calcium Levels With Coronary Artery Disease and Myocardial Infarction. JAMA. 2017;318:371-380 pubmed publisher
    ..Whether the risk of CAD associated with lifelong genetic exposure to increased serum calcium levels can be translated to a risk associated with short-term to medium-term calcium supplementation is unknown. ..
  4. Burgess S. Re: "credible mendelian randomization studies: approaches for evaluating the instrumental variable assumptions". Am J Epidemiol. 2012;176:456-7 pubmed publisher
  5. Hannon E, Weedon M, Bray N, O DONOVAN M, Mill J. Pleiotropic Effects of Trait-Associated Genetic Variation on DNA Methylation: Utility for Refining GWAS Loci. Am J Hum Genet. 2017;100:954-959 pubmed publisher
    ..We identified multiple examples of variable DNA methylation associated with GWAS variants for a range of complex traits, demonstrating the utility of this approach for refining genetic association signals. ..
  6. Nikolopoulos G, Bagos P, Tsangaris I, Tsiara C, Kopterides P, Vaiopoulos A, et al. The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis. Clin Chem Lab Med. 2014;52:937-50 pubmed publisher
    ..Further research is warranted to elucidate these interactions. ..
  7. Taylor A, Munafo M. Commentary: Does mortality from smoking have implications for future Mendelian randomization studies?. Int J Epidemiol. 2014;43:1483-6 pubmed publisher
  8. Dai J, Zhang X. Mendelian randomization studies for a continuous exposure under case-control sampling. Am J Epidemiol. 2015;181:440-9 pubmed publisher
  9. Hartwig F, Davies N, Hemani G, Davey Smith G. Two-sample Mendelian randomization: avoiding the downsides of a powerful, widely applicable but potentially fallible technique. Int J Epidemiol. 2016;45:1717-1726 pubmed publisher

More Information


  1. Dimitrakopoulou V, Tsilidis K, Haycock P, Dimou N, Al Dabhani K, Martin R, et al. Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study. BMJ. 2017;359:j4761 pubmed publisher
  2. Burgess S, Malarstig A. Using Mendelian randomization to assess and develop clinical interventions: limitations and benefits. J Comp Eff Res. 2013;2:209-12 pubmed publisher
  3. Zhan Y, Song C, Karlsson R, Tillander A, Reynolds C, Pedersen N, et al. Telomere Length Shortening and Alzheimer Disease--A Mendelian Randomization Study. JAMA Neurol. 2015;72:1202-3 pubmed publisher
  4. Gill D, Del Greco M F, Walker A, Srai S, Laffan M, Minelli C. The Effect of Iron Status on Risk of Coronary Artery Disease: A Mendelian Randomization Study-Brief Report. Arterioscler Thromb Vasc Biol. 2017;37:1788-1792 pubmed publisher
    ..08 per SD unit increase; 95% confidence interval, 1.01-1.16; P=0.034). This Mendelian randomization study supports the hypothesis that higher iron status reduces CAD risk. These findings may highlight a therapeutic target. ..
  5. Zhang B, Shu X, Delahanty R, Zeng C, Michailidou K, Bolla M, et al. Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization. J Natl Cancer Inst. 2015;107: pubmed publisher
    ..with individual-level data from 46325 case patients and 42482 control patients, we conducted a Mendelian randomization analysis using a genetic score that comprised 168 height-associated variants as an instrument...
  6. Haycock P, Burgess S, Nounu A, Zheng J, Okoli G, Bowden J, et al. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study. JAMA Oncol. 2017;3:636-651 pubmed publisher
    ..28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]). It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases. ..
  7. Richardson T, Zheng J, Davey Smith G, Timpson N, Gaunt T, Relton C, et al. Mendelian Randomization Analysis Identifies CpG Sites as Putative Mediators for Genetic Influences on Cardiovascular Disease Risk. Am J Hum Genet. 2017;101:590-602 pubmed publisher
    ..Integrating our results with expression quantitative trait loci data, we provide evidence that variation at these regulatory regions is likely to also influence gene expression levels at these loci. ..
  8. Swerdlow D, Holmes M, Kuchenbaecker K, Engmann J, Shah T, Sofat R, et al. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet. 2012;379:1214-24 pubmed publisher
  9. Bennett D, Holmes M. Mendelian randomisation in cardiovascular research: an introduction for clinicians. Heart. 2017;103:1400-1407 pubmed publisher
    ..The variety of the examples presented illustrates the importance of Mendelian randomisation in order to prioritise drug targets for cardiovascular research. ..
  10. Li X, Meng X, Timofeeva M, Tzoulaki I, Tsilidis K, Ioannidis J, et al. Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies. BMJ. 2017;357:j2376 pubmed publisher
  11. Shin M, Cho Y, Davey Smith G. Alcohol Consumption, Aldehyde Dehydrogenase 2 Gene Polymorphisms, and Cardiovascular Health in Korea. Yonsei Med J. 2017;58:689-696 pubmed publisher
    ..In conclusion, strategies that incorporate genetic information and provide an evidential basis from which to help people make informed decisions on alcohol consumption are urgently required. ..
  12. Nano J, Ghanbari M, Wang W, de Vries P, Dhana K, Muka T, et al. Epigenome-Wide Association Study Identifies Methylation Sites Associated With Liver Enzymes and Hepatic Steatosis. Gastroenterology. 2017;153:1096-1106.e2 pubmed publisher
    ..Our results provide new insights into epigenetic mechanisms associated with markers of liver function and hepatic steatosis, laying the groundwork for future diagnostic and therapeutic applications. ..
  13. Censin J, Nowak C, Cooper N, Bergsten P, Todd J, Fall T. Childhood adiposity and risk of type 1 diabetes: A Mendelian randomization study. PLoS Med. 2017;14:e1002362 pubmed publisher
    ..Using inverse-variance weighted Mendelian randomization analysis, we found support for an effect of childhood adiposity on T1D risk (odds ratio 1.32, 95% CI 1.06-1...
  14. Larsson S, Traylor M, Malik R, Dichgans M, Burgess S, Markus H. Modifiable pathways in Alzheimer's disease: Mendelian randomisation analysis. BMJ. 2017;359:j5375 pubmed publisher
    ..These results provide support that higher educational attainment is associated with a reduced risk of Alzheimer's disease. ..
  15. Wang L, Zhang Z. [Mendelian randomization approach, used for causal inferences]. Zhonghua Liu Xing Bing Xue Za Zhi. 2017;38:547-552 pubmed publisher
  16. Alharbi O, El Sohemy A. Lactose Intolerance (LCT-13910C>T) Genotype Is Associated with Plasma 25-Hydroxyvitamin D Concentrations in Caucasians: A Mendelian Randomization Study. J Nutr. 2017;147:1063-1069 pubmed publisher
    ..Increased risk of suboptimal concentrations of vitamin D was also observed among those with the CT genotype, suggesting an intermediate effect of the heterozygous genotype. ..
  17. Kizer J. A tangled threesome: adiponectin, insulin sensitivity, and adiposity: can Mendelian randomization sort out causality?. Diabetes. 2013;62:1007-9 pubmed publisher
  18. Paternoster L, Tilling K, Davey Smith G. Genetic epidemiology and Mendelian randomization for informing disease therapeutics: Conceptual and methodological challenges. PLoS Genet. 2017;13:e1006944 pubmed publisher
    ..One reason for this, we suggest, is that GWAS, to date, have generally not focused on phenotypes that directly relate to the progression of disease and thus speak to disease treatment...
  19. Tillmann T, Vaucher J, Okbay A, Pikhart H, Peasey A, Kubinova R, et al. Education and coronary heart disease: mendelian randomisation study. BMJ. 2017;358:j3542 pubmed publisher
    ..Potential mechanisms could include smoking, body mass index, and blood lipids. In conjunction with the results from studies with other designs, these findings suggest that increasing education may result in substantial health benefits. ..
  20. Pierce B, Tong L, Argos M, Gao J, Farzana J, Roy S, et al. Arsenic metabolism efficiency has a causal role in arsenic toxicity: Mendelian randomization and gene-environment interaction. Int J Epidemiol. 2013;42:1862-71 pubmed publisher
    ..exposure and metabolism in a wide array of health conditions.Developing interventions that increase arsenic metabolism efficiency are likely to reduce the impact of arsenic exposure on health. ..
  21. Boef A, le Cessie S, Dekkers O. Mendelian randomization studies in the elderly. Epidemiology. 2015;26:e15-6 pubmed publisher
  22. Larsson S, Scott R, Traylor M, Langenberg C, Hindy G, Melander O, et al. Type 2 diabetes, glucose, insulin, BMI, and ischemic stroke subtypes: Mendelian randomization study. Neurology. 2017;89:454-460 pubmed publisher
    ..This study provides support that T2D may be causally associated with large artery stroke. ..
  23. Lindstrom S, Germain M, Crous Bou M, Smith E, Morange P, van Hylckama Vlieg A, et al. Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study. Hum Genet. 2017;136:897-902 pubmed publisher
    ..93 per standard deviation increase in BMI, P = 5.8 × 10-6). Our study provides evidence for a causal relationship between high BMI and risk of VTE. Reducing obesity levels will likely result in lower incidence in VTE. ..
  24. Benn M, Nordestgaard B, Frikke Schmidt R, Tybjærg Hansen A. Low LDL cholesterol, PCSK9 and HMGCR genetic variation, and risk of Alzheimer's disease and Parkinson's disease: Mendelian randomisation study. BMJ. 2017;357:j1648 pubmed publisher
  25. Burgess S, Butterworth A, Malarstig A, Thompson S. Use of Mendelian randomisation to assess potential benefit of clinical intervention. BMJ. 2012;345:e7325 pubmed publisher
  26. Reed Z, Micali N, Bulik C, Davey Smith G, Wade K. Assessing the causal role of adiposity on disordered eating in childhood, adolescence, and adulthood: a Mendelian randomization analysis. Am J Clin Nutr. 2017;106:764-772 pubmed publisher
    ..These results encourage an exploration of the ways to break the causal chain between these complex phenotypes, which could inform and prevent disordered eating problems in adolescence. ..
  27. Nordestgaard L, Tybjærg Hansen A, Nordestgaard B, Frikke Schmidt R. Body Mass Index and Risk of Alzheimer's Disease: A Mendelian Randomization Study of 399,536 Individuals. J Clin Endocrinol Metab. 2017;102:2310-2320 pubmed publisher
    ..Recently, data on 2,000,000 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...
  28. Noyce A, Kia D, Hemani G, Nicolas A, Price T, de Pablo Fernández E, et al. Estimating the causal influence of body mass index on risk of Parkinson disease: A Mendelian randomisation study. PLoS Med. 2017;14:e1002314 pubmed publisher
    ..The mechanism underlying this apparent protective effect warrants further study. ..
  29. Carreras Torres R, Johansson M, Haycock P, Wade K, Relton C, Martin R, et al. Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study. PLoS ONE. 2017;12:e0177875 pubmed publisher
    ..Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer...
  30. Voora D, Shah S. Pharmacometabolomics Meets Genetics: A "Natural" Clinical Trial of Statin Effects. J Am Coll Cardiol. 2016;67:1211-1213 pubmed publisher
  31. Haycock P, Burgess S, Wade K, Bowden J, Relton C, Davey Smith G. Best (but oft-forgotten) practices: the design, analysis, and interpretation of Mendelian randomization studies. Am J Clin Nutr. 2016;103:965-78 pubmed
    ..Although impossible to prove causality with any single approach, MR is a highly cost-effective strategy for prioritizing intervention targets for disease prevention and for strengthening the evidence base for public health policy. ..
  32. Di Lena P, Martelli P, Fariselli P, Casadio R. NET-GE: a novel NETwork-based Gene Enrichment for detecting biological processes associated to Mendelian diseases. BMC Genomics. 2015;16 Suppl 8:S6 pubmed publisher
    ..Our procedure is effective even when the size of the input protein set is small, requiring at least two input proteins. ..
  33. Burgess S, Thompson S. Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects. Am J Epidemiol. 2015;181:251-60 pubmed publisher
    A conventional Mendelian randomization analysis assesses the causal effect of a risk factor on an outcome by using genetic variants that are solely associated with the risk factor of interest as instrumental variables...
  34. Eriksson J, Haring R, Grarup N, Vandenput L, Wallaschofski H, Lorentzen E, et al. Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis. PLoS ONE. 2017;12:e0176277 pubmed publisher
    ..Our results suggest that there is a causal effect of BMI on serum testosterone in men. Population level interventions to reduce BMI are expected to increase serum testosterone in men. ..
  35. Pierce B, Burgess S. Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am J Epidemiol. 2013;178:1177-84 pubmed publisher
    ..Various approaches for confidence interval calculation are considered. These results have important implications for reducing the costs and increasing the feasibility of MR studies. ..
  36. Kamstrup P, Hung M, Witztum J, Tsimikas S, Nordestgaard B. Oxidized Phospholipids and Risk of Calcific Aortic Valve Disease: The Copenhagen General Population Study. Arterioscler Thromb Vasc Biol. 2017;37:1570-1578 pubmed publisher
    ..27 (95% CI, 1.16-1.39), 1.13 (95% CI, 1.08-1.18), and 1.11 (95% CI, 1.06-1.17). OxPL-apoB and OxPL-apo(a) are novel genetic and potentially causal risk factors for CAVD and may explain the association of lipoprotein(a) with CAVD. ..
  37. . Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis. Lancet Diabetes Endocrinol. 2015;3:243-53 pubmed publisher
    ..The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. ..
  38. Relton C, Davey Smith G. Mendelian randomization: applications and limitations in epigenetic studies. Epigenomics. 2015;7:1239-43 pubmed publisher
  39. Burgess S, Dudbridge F, Thompson S. Re: "Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects". Am J Epidemiol. 2015;181:290-1 pubmed publisher
  40. Burgess S, Davey Smith G. Mendelian Randomization Implicates High-Density Lipoprotein Cholesterol-Associated Mechanisms in Etiology of Age-Related Macular Degeneration. Ophthalmology. 2017;124:1165-1174 pubmed publisher
    ..Some genetic evidence suggests that HDL-cholesterol is a causal risk factor for AMD risk and that increasing HDL-cholesterol (particularly via CETP inhibition) will increase AMD risk. ..
  41. Kronenberg F. Genetic variation in HDL-related genes and the association with cardiovascular disease: HDL particles as chameleons of lipoprotein metabolism. J Intern Med. 2011;270:128-31 pubmed publisher
  42. Burgess S, Timpson N, Ebrahim S, Davey Smith G. Mendelian randomization: where are we now and where are we going?. Int J Epidemiol. 2015;44:379-88 pubmed publisher
  43. Würtz P, Kangas A, Soininen P, Lawlor D, Davey Smith G, Ala Korpela M. Quantitative Serum Nuclear Magnetic Resonance Metabolomics in Large-Scale Epidemiology: A Primer on -Omic Technologies. Am J Epidemiol. 2017;186:1084-1096 pubmed publisher
  44. Wensley F, Gao P, Burgess S, Kaptoge S, Di Angelantonio E, Shah T, et al. Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data. BMJ. 2011;342:d548 pubmed publisher
    ..001 for difference). Human genetic data indicate that C reactive protein concentration itself is unlikely to be even a modest causal factor in coronary heart disease. ..
  45. Ference B, Kastelein J, Ginsberg H, Chapman M, Nicholls S, Ray K, et al. Association of Genetic Variants Related to CETP Inhibitors and Statins With Lipoprotein Levels and Cardiovascular Risk. JAMA. 2017;318:947-956 pubmed publisher
    ..The clinical benefit of lowering LDL-C levels may therefore depend on the corresponding reduction in apoB-containing lipoprotein particles. ..
  46. Noordam R, Hamer M, Pardo L, van der Nat T, Kiefte de Jong J, Kayser M, et al. No Causal Association between 25-Hydroxyvitamin D and Features of Skin Aging: Evidence from a Bidirectional Mendelian Randomization Study. J Invest Dermatol. 2017;137:2291-2297 pubmed publisher
    ..05). Our study did not indicate that associations between 25-hydroxyvitamin D and features of skin aging are causal. ..
  47. Dale C, Fatemifar G, Palmer T, White J, Prieto Merino D, Zabaneh D, et al. Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis. Circulation. 2017;135:2373-2388 pubmed publisher
    ..Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity. ..
  48. Zhan Y, Karlsson I, Karlsson R, Tillander A, Reynolds C, Pedersen N, et al. Exploring the Causal Pathway From Telomere Length to Coronary Heart Disease: A Network Mendelian Randomization Study. Circ Res. 2017;121:214-219 pubmed publisher
    ..Network Mendelian randomization analysis-an approach using genetic variants as the instrumental variables for both the exposure and mediator ..
  49. Lauritzen L, Sørensen L, Harsløf L, Ritz C, Stark K, Astrup A, et al. Mendelian randomization shows sex-specific associations between long-chain PUFA-related genotypes and cognitive performance in Danish schoolchildren. Am J Clin Nutr. 2017;106:88-95 pubmed publisher
    ..This may be a consequence of increased endogenous DHA synthesis in infancy but not at school-age. This trial was registered at as NCT01457794. ..