publication . Article . Other literature type . 2017

Recent Developments in Mendelian Randomization Studies

Maria Carolina Borges; George Davey Smith; Gibran Hemani;
Open Access English
  • Published: 22 Nov 2017 Journal: Current Epidemiology Reports, volume 4, issue 4, pages 330-345 (eissn: 2196-2995, Copyright policy)
  • Publisher: Springer International Publishing
  • Country: United Kingdom
Abstract
Purpose of Review<br/>Mendelian randomization (MR) is a strategy for evaluating causality in observational epidemiological studies. MR exploits the fact that genotypes are not generally susceptible to reverse causation and confounding, due to their fixed nature and Mendel’s First and Second Laws of Inheritance. MR has the potential to provide information on causality in many situations where randomized controlled trials are not possible, but the results of MR studies must be interpreted carefully to avoid drawing erroneous conclusions.<br/><br/>Recent Findings<br/>In this review, we outline the principles behind MR, as well as assumptions and limitations of the ...
Subjects
free text keywords: /dk/atira/pure/researchoutput/pubmedpublicationtype/D016428, Journal Article, /dk/atira/pure/researchoutput/pubmedpublicationtype/D016454, Review, Genetic Epidemiology (C Amos, Section Editor), Mendelian randomization, Databases and automation tools for causal inference, Hypothesis-free causality, Drug development, Disease progression
Related Organizations
106 references, page 1 of 8

1.Davey SG, Ebrahim S. Data dredging, bias, or confounding. BMJ. 2002;325(7378):1437–8.

Lawlor, DA, Harbord, RM, Sterne, JAC, Timpson, N, Davey Smith, G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008; 27 (8): 1133-1163 [OpenAIRE] [PubMed] [DOI]

3.Burgess S, Small DS, Thompson SG. A review of instrumental variable estimators for Mendelian randomization. Stat Methods Med Res [Internet]. 2015 ; Available from: 10.1177/0962280215597579.

Holmes, MV, Ala-Korpela, M, Davey, SG. Mendelian randomization in cardiometabolic disease: challenges in evaluating causality. Nat Rev Cardiol. 2017; 14 (10): 577-590 [OpenAIRE] [PubMed] [DOI]

Würtz, P, Wang, Q, Soininen, P, Kangas, AJ, Fatemifar, G, Tynkkynen, T. Metabolomic profiling of statin use and genetic inhibition of HMG-CoA reductase. J Am Coll Cardiol. 2016; 67 (10): 1200-1210 [OpenAIRE] [PubMed] [DOI]

Ference, BA, Majeed, F, Penumetcha, R, Flack, JM, Brook, RD. Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both: a 2 × 2 factorial Mendelian randomization study. J Am Coll Cardiol. 2015; 65 (15): 1552-1561 [OpenAIRE] [PubMed] [DOI]

7.Myocardial Infarction Genetics Consortium Investigators, Stitziel NO, Won HH, Morrison AC, Peloso GM, Do R, Lange LA, et al. Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med. 2014;371(22):2072–82.

Cohen, JC, Boerwinkle, E, Mosley, TH, Hobbs, HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006; 354 (12): 1264-1272 [PubMed] [DOI]

Navarese, EP, Kolodziejczak, M, Schulze, V, Gurbel, PA, Tantry, U, Lin, Y. Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia: a systematic review and meta-analysis. Ann Intern Med. 2015; 163 (1): 40-51 [OpenAIRE] [PubMed] [DOI]

Wensley, F, Gao, P, Burgess, S, Kaptoge, S, Di Angelantonio, E. Association between C reactive protein and coronary heart disease: Mendelian randomisation analysis based on individual participant data. BMJ. 2011; 342: d548 [OpenAIRE] [PubMed] [DOI]

Zacho, J, Tybjaerg-Hansen, A, Jensen, JS, Grande, P, Sillesen, H, Nordestgaard, BG. Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med. 2008; 359 (18): 1897-1908 [OpenAIRE] [PubMed] [DOI]

Polfus, LM, Gibbs, RA, Boerwinkle, E. Coronary heart disease and genetic variants with low phospholipase A2 activity. N Engl J Med. 2015; 372 (3): 295-296 [OpenAIRE] [PubMed] [DOI]

Millwood, IY, Bennett, DA, Walters, RG, Clarke, R, Waterworth, D, Johnson, T. Lipoprotein-associated phospholipase A2 loss-of-function variant and risk of vascular diseases in 90,000 Chinese adults. J Am Coll Cardiol. 2016; 67 (2): 230-231 [OpenAIRE] [PubMed] [DOI]

Swerdlow, DI, Holmes, MV, Kuchenbaecker, KB, Engmann, JEL, Shah, T. The interleukin-6 receptor as a target for prevention of coronary heart disease: a Mendelian randomisation analysis. Lancet. 2012; 379 (9822): 1214-1224 [OpenAIRE] [PubMed] [DOI]

Swerdlow, DI, Preiss, D, Kuchenbaecker, KB, Holmes, MV, Engmann, JEL, Shah, T. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet. 2015; 385 (9965): 351-361 [OpenAIRE] [PubMed] [DOI]

106 references, page 1 of 8
Abstract
Purpose of Review<br/>Mendelian randomization (MR) is a strategy for evaluating causality in observational epidemiological studies. MR exploits the fact that genotypes are not generally susceptible to reverse causation and confounding, due to their fixed nature and Mendel’s First and Second Laws of Inheritance. MR has the potential to provide information on causality in many situations where randomized controlled trials are not possible, but the results of MR studies must be interpreted carefully to avoid drawing erroneous conclusions.<br/><br/>Recent Findings<br/>In this review, we outline the principles behind MR, as well as assumptions and limitations of the ...
Subjects
free text keywords: /dk/atira/pure/researchoutput/pubmedpublicationtype/D016428, Journal Article, /dk/atira/pure/researchoutput/pubmedpublicationtype/D016454, Review, Genetic Epidemiology (C Amos, Section Editor), Mendelian randomization, Databases and automation tools for causal inference, Hypothesis-free causality, Drug development, Disease progression
Related Organizations
106 references, page 1 of 8

1.Davey SG, Ebrahim S. Data dredging, bias, or confounding. BMJ. 2002;325(7378):1437–8.

Lawlor, DA, Harbord, RM, Sterne, JAC, Timpson, N, Davey Smith, G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008; 27 (8): 1133-1163 [OpenAIRE] [PubMed] [DOI]

3.Burgess S, Small DS, Thompson SG. A review of instrumental variable estimators for Mendelian randomization. Stat Methods Med Res [Internet]. 2015 ; Available from: 10.1177/0962280215597579.

Holmes, MV, Ala-Korpela, M, Davey, SG. Mendelian randomization in cardiometabolic disease: challenges in evaluating causality. Nat Rev Cardiol. 2017; 14 (10): 577-590 [OpenAIRE] [PubMed] [DOI]

Würtz, P, Wang, Q, Soininen, P, Kangas, AJ, Fatemifar, G, Tynkkynen, T. Metabolomic profiling of statin use and genetic inhibition of HMG-CoA reductase. J Am Coll Cardiol. 2016; 67 (10): 1200-1210 [OpenAIRE] [PubMed] [DOI]

Ference, BA, Majeed, F, Penumetcha, R, Flack, JM, Brook, RD. Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both: a 2 × 2 factorial Mendelian randomization study. J Am Coll Cardiol. 2015; 65 (15): 1552-1561 [OpenAIRE] [PubMed] [DOI]

7.Myocardial Infarction Genetics Consortium Investigators, Stitziel NO, Won HH, Morrison AC, Peloso GM, Do R, Lange LA, et al. Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med. 2014;371(22):2072–82.

Cohen, JC, Boerwinkle, E, Mosley, TH, Hobbs, HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006; 354 (12): 1264-1272 [PubMed] [DOI]

Navarese, EP, Kolodziejczak, M, Schulze, V, Gurbel, PA, Tantry, U, Lin, Y. Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia: a systematic review and meta-analysis. Ann Intern Med. 2015; 163 (1): 40-51 [OpenAIRE] [PubMed] [DOI]

Wensley, F, Gao, P, Burgess, S, Kaptoge, S, Di Angelantonio, E. Association between C reactive protein and coronary heart disease: Mendelian randomisation analysis based on individual participant data. BMJ. 2011; 342: d548 [OpenAIRE] [PubMed] [DOI]

Zacho, J, Tybjaerg-Hansen, A, Jensen, JS, Grande, P, Sillesen, H, Nordestgaard, BG. Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med. 2008; 359 (18): 1897-1908 [OpenAIRE] [PubMed] [DOI]

Polfus, LM, Gibbs, RA, Boerwinkle, E. Coronary heart disease and genetic variants with low phospholipase A2 activity. N Engl J Med. 2015; 372 (3): 295-296 [OpenAIRE] [PubMed] [DOI]

Millwood, IY, Bennett, DA, Walters, RG, Clarke, R, Waterworth, D, Johnson, T. Lipoprotein-associated phospholipase A2 loss-of-function variant and risk of vascular diseases in 90,000 Chinese adults. J Am Coll Cardiol. 2016; 67 (2): 230-231 [OpenAIRE] [PubMed] [DOI]

Swerdlow, DI, Holmes, MV, Kuchenbaecker, KB, Engmann, JEL, Shah, T. The interleukin-6 receptor as a target for prevention of coronary heart disease: a Mendelian randomisation analysis. Lancet. 2012; 379 (9822): 1214-1224 [OpenAIRE] [PubMed] [DOI]

Swerdlow, DI, Preiss, D, Kuchenbaecker, KB, Holmes, MV, Engmann, JEL, Shah, T. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet. 2015; 385 (9965): 351-361 [OpenAIRE] [PubMed] [DOI]

106 references, page 1 of 8
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