Mendelian Randomization versus Path Models: Making Causal Inferences in Genetic Epidemiology

Human Heredity

Volumn 79, Issue 3-4, 2015, Pages 194-204

  Ziegler, Andreas ^a,b,c,d   Mwambi, Henry ^d   König, Inke R ^a,c  

^a UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

^b UNIVERSITY OF LÜBECK   (Germany)

^c Deutsches Zentrum für Herz Kreislauf Forschung   (Germany)

^d UNIVERSITY OF KWAZULU NATAL   (South Africa)

Author keywords

'Omics'; Causality; Mendelian randomization; Path model; Structural equation model

Indexed keywords

C REACTIVE PROTEIN; HEMOGLOBIN A1C; LOW DENSITY LIPOPROTEIN CHOLESTEROL; VERY LOW DENSITY LIPOPROTEIN;

ARTICLE; CAUSAL MODELING; COMPARATIVE STUDY; CORONARY ARTERY DISEASE; DEPENDENT VARIABLE; DIABETES MELLITUS; ENVIRONMENTAL FACTOR; GENETIC ASSOCIATION; GENETIC EPIDEMIOLOGY; GENOTYPING TECHNIQUE; HAPLOTYPE; HUMAN; INSULIN RESISTANCE; MENDELIAN RANDOMIZATION ANALYSIS; OUTCOME VARIABLE; PATH MODELING; SINGLE NUCLEOTIDE POLYMORPHISM; BIOLOGICAL MODEL; GENETIC PREDISPOSITION; GENETICS; METABOLISM; MOLECULAR EPIDEMIOLOGY;

CHOLESTEROL, LDL; CORONARY ARTERY DISEASE; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MENDELIAN RANDOMIZATION ANALYSIS; MODELS, GENETIC; MOLECULAR EPIDEMIOLOGY; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84937865632     PISSN: 00015652     EISSN: 14230062     Source Type: Journal    
DOI: 10.1159/000381338     Document Type: Article

References (49)

1. Katan MB: Apolipoprotein E isoforms, serum cholesterol, and cancer. Lancet 1986; 1: 507-508.
2. Tobin MD, Minelli C, Burton PR, Thompson JR: Commentary: development of Mendelian randomization: from hypothesis test to 'Mendelian deconfounding'. Int J Epidemiol 2004; 33: 26-29.
3. Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G: Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med 2008; 27: 1133-1163.
4. Bochud M: On the use of Mendelian randomization to infer causality in observational epidemiology. Eur Heart J 2008; 29: 2456-2457.
5. Vander Weele TJ, Tchetgen Tchetgen EJ, Cornelis M, Kraft P: Methodological challenges in mendelian randomization. Epidemiology 2014; 25: 427-435.
6. Ziegler A, Pahlke F, König IR: Comments on Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med 2008; 27: 2974-2976.
7. Jansen H, Samani NJ, Schunkert H: Mendelian randomization studies in coronary artery disease. Eur Heart J 2014; 35: 1917-1924.
8. Sheehan NA, Meng S, Didelez V: Mendelian randomisation: a tool for assessing causality in observational epidemiology. Methods Mol Biol 2011; 713: 153-166.
9. Cookson W, Liang L, Abecasis G, Moffatt M, Lathrop M: Mapping complex disease traits with global gene expression. Nat Rev Genet 2009; 10: 184-194.
10. Crick F: Central dogma of molecular biology. Nature 1970; 227: 561-563.
11. Hill AB: The environment and disease: association or causation? Proc R Soc Med 1965; 58: 295-300.
12. Wright S: Correlation and causation. J Agricult Res 1921; 20: 557-585.
13. Hoyle RH (ed): Handbook of Structural Equation Modeling. New York, Guilford Press, 2012.
14. Samani NJ, Braund PS, Erdmann J, Götz A, Tomaszewski M, Linsel-Nitschke P, Hajat C, Mangino M, Hengstenberg C, Stark K, Ziegler A, Caulfield M, Burton PR, Schunkert H, Tobin MD: The novel genetic variant predisposing to coronary artery disease in the region of the PSRC1 and CELSR2 genes on chromosome 1 associates with serum cholesterol. J Mol Med 2008; 86: 1233-1241.
15. Linsel-Nitschke P, Götz A, Erdmann J, Brænne I, Braund P, Hengstenberg C, Stark K, Fischer M, Schreiber S, El Mokhtari NE, Schaefer A, Schrezenmeier J, Rubin D, Hinney A, Reinehr T, Roth C, Ortlepp J, Hanrath P, Hall AS, Mangino M, Lieb W, Lamina C, Heid IM, Doering A, Gieger C, Peters A, Meitinger T, Wichmann H-E, König IR, Ziegler A, Kronenberg F, Samani NJ, Schunkert H; Wellcome Trust Case Control Consortium (WTCCC); Cardiogenics Consortium: Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease - a Mendelian randomisation study. PLoS One 2008; 3:e2986.
16. Brunner EJ, Kivimaki M, Witte DR, Lawlor DA, Davey Smith G, Cooper JA, Miller M, Lowe GD, Rumley A, Casas JP, Shah T, Humphries SE, Hingorani AD, Marmot MG, Timpson NJ, Kumari M: Inflammation, insulin resistance, and diabetes-Mendelian randomization using CRP haplotypes points upstream. PLoS Med 2008; 5:e155.
17. Bochud M, Rousson V: Usefulness of Mendelian randomization in observational epidemiology. Int J Environ Res Public Health 2010; 7: 711-728.
18. Burgess S: Re: 'credible mendelian randomization studies: approaches for evaluating the instrumental variable assumptions'. Am J Epidemiol 2012; 176: 456-457.
19. Smith GD, Ebrahim S: Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol 2004; 33: 30-42.
20. Smith GD, Hemani G: Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet 2014; 23:R89-R98.
21. Burgess S, Thompson SG: Use of allele scores as instrumental variables for Mendelian randomization. Int J Epidemiol 2013; 42: 1134-1144.
22. Ference BA, Yoo W, Alesh I, Mahajan N, Mirowska KK, Mewada A, Kahn J, Afonso L, Williams KA Sr, Flack JM: Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol 2012; 60: 2631-2639.
23. Relton CL, Smith GD: Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease. Int J Epidemiol 2012; 41: 161-176.
24. Saccone NL, Saccone SF, Hinrichs AL, Stitzel JA, Duan W, Pergadia ML, Agrawal A, Breslau N, Grucza RA, Hatsukami D, Johnson EO, Madden PA, Swan GE, Wang JC, Goate AM, Rice JP, Bierut LJ: Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genes. Am J Med Genet B Neuropsychiatr Genet 2009; 150B:453-466.
25. Breitling LP, Salzmann K, Rothenbacher D, Burwinkel B, Brenner H: Smoking, F2RL3 methylation, and prognosis in stable coronary heart disease. Eur Heart J 2012; 33: 2841-2848.
26. Bell JT, Pai AA, Pickrell JK, Gaffney DJ, Pique-Regi R, Degner JF, Gilad Y, Pritchard JK: DNA methylation patterns associate with genetic and gene expression variation in Hap-Map cell lines. Genome Biol 2011; 12:R10.
27. Shipley B: Cause and Correlation in Biology: A User's Guide to Path Analysis, Structural Equations and Causal Inference. Cambridge, Cambridge University Press, 2000.
28. Foster JJ, Barkus E, Yavorsky C: Understanding and Using Advanced Statistics. London, Sage, 2006.
29. Stanton LW, Garrard LJ, Damm D, Garrick BL, Lam A, Kapoun AM, Zheng Q, Protter AA, Schreiner GF, White RT: Altered patterns of gene expression in response to myocardial infarction. Circ Res 2000; 86: 939-945.
30. Keller T, Zeller T, Peetz D, Tzikas S, Roth A, Czyz E, Bickel C, Baldus S, Warnholtz A, Frohlich M, Sinning CR, Eleftheriadis MS, Wild PS, Schnabel RB, Lubos E, Jachmann N, Genth-Zotz S, Post F, Nicaud V, Tiret L, Lackner KJ, Munzel TF, Blankenberg S: Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med 2009; 361: 868-877.
31. Katan MB: Commentary: Mendelian Randomization, 18 years on. Int J Epidemiol 2004; 33: 10-11.
32. Vander Weele TJ: Invited commentary: structural equation models and epidemiologic analysis. Am J Epidemiol 2012; 176: 608-612.
33. Cole DA, Preacher KJ: Manifest variable path analysis: potentially serious and misleading consequences due to uncorrected measurement error. Psychol Methods 2014; 19: 300-315.
34. Amemiya T: Tobit models - a survey. J Econom 1984; 24: 3-61.
35. Teixeira-Pinto A, Normand SL: Correlated bivariate continuous and binary outcomes: issues and applications. Stat Med 2009; 28: 1753-1773.
36. Browne MW, Arminger G: Specification and estimation of mean- and covariance-structure models; in Arminger G, Clogg CC, Sobel ME (eds): Handbook of Statistical Modeling for the Social and Behavioral Sciences. New York, Plenum Press, 1995, pp 185-249.
37. Muthén LK, Muthén BO: Mplus User's Guide, ed 7. Los Angeles, Muthén & Muthén, 2012.
38. Liu J, Pei Y, Papasian CJ, Deng HW: Bivariate association analyses for the mixture of continuous and binary traits with the use of extended generalized estimating equations. Genet Epidemiol 2009; 33: 217-227.
39. Fitzmaurice GM, Laird NM: Regression models for a bivariate discrete and continuous outcome with clustering. J Am Stat Assoc 1995; 90: 845-852.
40. Ziegler A, Arminger G: Analyzing the employment status with panel data from the GSOEP - a comparison of the MECOSA and the GEE1 approach for marginal models. Quart J Econom Res 1995; 64: 72-80.
41. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110: 227-239.
42. Linsel-Nitschke P, Heeren J, Aherrahrou Z, Bruse P, Gieger C, Illig T, Prokisch H, Heim K, Doering A, Peters A, Meitinger T, Wichmann HE, Hinney A, Reinehr T, Roth C, Ortlepp JR, Soufi M, Sattler AM, Schaefer J, Stark K, Hengstenberg C, Schaefer A, Schreiber S, Kronenberg F, Samani NJ, Schunkert H, Erdmann J: Genetic variation at chromosome 1p13.3 affects sortilin mRNA expression, cellular LDL-uptake and serum LDL levels which translates to the risk of coronary artery disease. Atherosclerosis 2010; 208: 183-189.
43. Musunuru K, Strong A, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV, Li X, Li H, Kuperwasser N, Ruda VM, Pirruccello JP, Muchmore B, Prokunina-Olsson L, Hall JL, Schadt EE, Morales CR, Lund-Katz S, Phillips MC, Wong J, Cantley W, Racie T, Ejebe KG, Orho-Melander M, Melander O, Koteliansky V, Fitzgerald K, Krauss RM, Cowan CA, Kathiresan S, Rader DJ: From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 2010; 466: 714-719.
44. Linsel-Nitschke P, Samani NJ, Schunkert H: Sorting out cholesterol and coronary artery disease. N Engl J Med 2010; 363: 2462-2463.
45. Smith GD: Random allocation in observational data: how small but robust effects could facilitate hypothesis-free causal inference. Epidemiology 2011; 22: 460-463; discussion 467-468.
46. Neto EC, Keller MP, Attie AD, Yandell BS: Causal graphical models in systems genetics: a unified framework for joint inference of causal network and genetic architecture for correlated phenotypes. Ann Appl Stat 2010; 4: 320-339.
47. Peng CH, Jiang YZ, Tai AS, Liu CB, Peng SC, Liao CT, Yen TC, Hsieh WP: Causal inference of gene regulation with subnetwork assembly from genetical genomics data. Nucleic Acids Res 2014; 42: 2803-2819.
48. Voight BF, Peloso GM, Orho-Melander M, et al.: Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 2012; 380: 572-580.
49. Fitze G, Cramer J, Ziegler A, Schierz M, Schreiber M, Kuhlisch E, Roesner D, Schackert HK: Association between c135G/A genotype and RET proto-oncogene germline mutations and phenotype of Hirschsprung's disease. Lancet 2002; 359: 1200-1205.