Lifetime body mass index and later atherosclerosis risk in young adults: Examining causal links using Mendelian randomization in the Cardiovascular Risk in Young Finns study

European Heart Journal

Volumn 29, Issue 20, 2008, Pages 2552-2560

  Kivimäki, Mika ^a,b   Smith, George Davey ^c   Timpson, Nic J ^c,d   Lawlor, Debbie A ^c   Batty, G David ^e   Kähönen, Mika ^f   Juonala, Markus ^g,h   Rönnemaa, Tapani ^f   Viikari, Jorma S A ^g   Lehtimäki, Terho ^f   Raitakari, Olli T ^g,h  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b FINNISH INSTITUTE OF OCCUPATIONAL HEALTH   (Finland)

^c UNIVERSITY OF BRISTOL   (United Kingdom)

^d UNIVERSITY OF OXFORD   (United Kingdom)

^e UNIVERSITY OF GLASGOW   (United Kingdom)

^f TAMPERE UNIVERSITY HOSPITAL   (Finland)

^g UNIVERSITY OF TURKU   (Finland)

^h UNIVERSITY OF TURKU   (Finland)

Author keywords

Atherosclerosis; Body mass index; Mendelian randomization; Variation (genetics)

Indexed keywords

ADOLESCENT; ADULT; ADULTHOOD; ALLELE; ARTICLE; ATHEROSCLEROSIS; BODY MASS; CARDIOVASCULAR RISK; CAROTID ARTERY; CAUSAL ATTRIBUTION; CHILD; CHILDHOOD; CONTROLLED STUDY; DIET RESTRICTION; FEMALE; FINLAND; GENE DOSAGE; GENETIC POLYMORPHISM; GENETIC RISK; GENETIC VARIABILITY; GLUCOSE BLOOD LEVEL; HUMAN; HUMAN EXPERIMENT; INTIMA; LIFESPAN; MALE; PHENOTYPE; PLEIOTROPY; PRIORITY JOURNAL; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM; SYSTOLIC BLOOD PRESSURE;

ADOLESCENT; ADULT; ATHEROSCLEROSIS; BLOOD PRESSURE; BODY MASS INDEX; CAROTID ARTERY, COMMON; CHILD; CHILD, PRESCHOOL; CONFOUNDING FACTORS (EPIDEMIOLOGY); EPIDEMIOLOGIC METHODS; FEMALE; FINLAND; GENETIC VARIATION; GENOTYPE; HUMANS; MALE; PHENOTYPE; POLYMORPHISM, GENETIC; PROTEINS; SOCIOECONOMIC FACTORS; TUNICA INTIMA; TUNICA MEDIA; YOUNG ADULT;

EID: 54149096173     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehn252     Document Type: Article

References (48)

1. Davey Smith G, Ebrahim S. Data dredging, bias, or confounding. Br Med J 2002;325:1437-1438.
2. Duff GL, McMillan GC. Pathology of atherosclerosis. Am J Med 1951;11:92-108.
3. Davey Smith G, Ebrahim S. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol 2003;32:1-22.
4. Ebrahim S, Davey Smith G. Mendelian randomization: can genetic epidemiology help redress the failures of observational epidemiology? Hum Genet 2007;123:15-33.
5. 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 2007;27:1133-1163.
6. Hingorani A, Humphries S. Nature's randomised trials. Lancet 2005;366:1906-1908.
7. Raitakari OT, Juonala M, Kähönen M, Taittonen L, Laitinen T, Mäki-Torkko N, Järvisalo MJ, Uhari M, Jokinen E, Rönnemaa T, Åkerblom HK, Viikari JS. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns study. JAMA 2003;290:2277-2283.
8. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Järvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Davey Smith G, Hattersley AT, McCarthy MI. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007;316:889- 894.
9. Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, Najjar S, Nagaraja R, Orrú M, Usala G, Dei M, Lai S, Maschio A, Busonero F, Mulas A, Ehret GB, Fink AA, Weder AB, Cooper RS, Galan P, Chakravarti A, Schlessinger D, Cao A, Lakatta E, Abecasis GR. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007;3:e115.
10. Dina C, Meyre D, Gallina S, Durand E, Körner A, Jacobson P, Carlsson LM, Kiess W, Vatin V, Lecoeur C, Delplanque J, Vaillant E, Pattou F, Ruiz J, Weill J, Levy-Marchal C, Horber F, Potoczna N, Hercberg S, Le Stunff C, Bougnères P, Kovacs P, Marre M, Balkau B, Cauchi S, Chèvre JC, Froguel P. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 2007;39:724-726.
11. Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, Erdos MR, Stringham HM, Chines PS, Jackson AU, Prokunina-Olsson L, Ding CJ, Swift AJ, Narisu N, Hu T, Pruim R, Xiao R, Li XY, Conneely KN, Riebow NL, Sprau AG, Tong M, White PP, Hetrick KN, Barnhart MW, Bark CW, Goldstein JL, Watkins L, Xiang F, Saramies J, Buchanan TA, Watanabe RM, Valle TT, Kinnunen L, Abecasis GR, Pugh EW, Doheny KF, Bergman RN, Tuomilehto J, Collins FS, Boehnke M. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 2007;316:1341-1345.
12. Cardon LR, Palmer LJ. Population stratification and spurious allelic association. Lancet 2003;361:598-604.
13. Åkerblom HK, Uhari M, Pesonen E, Dahl M, Kaprio EA, Nuutinen EM, Uhari M, Pietikäinen M, Salo MK, Aromaa A, Kannas L, Keltikangas- Järvinen L, Kuusela V, Räsänen L, Rönnemaa T, Knip M, Telama R, Välimäki I, Pyörälä K, Viikari J. Cardiovascular Risk in Young Finns. Ann Med 1991;23:35-39.
14. Livak KJ. Allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Genet Anal 1999;14:143-149.
15. Yang X, Telama R, Leskinen E, Mansikkaniemi K, Viikari J, Raitakari OT. Testing a model of physical activity and obesity tracking from youth to adulthood: the cardiovascular risk in young Finns study. Int J Obes (Lond) 2007;31:521-527.
16. Kivimäki M, Lawlor DA, Davey Smith G, Keltikangas-Järvinen L, Elovainio M, Vahtera J, Pulkki-Råback L, Taittonen L, Viikari JS, Raitakari OT. Early socioeconomic position and blood pressure in childhood and adulthood: the Cardiovascular Risk in Young Finns study. Hypertension 2006;47:39-44.
17. Uhari M. Evaluation of the measurement of children's blood pressure in an epidemiological multicentre study. Acta Paediatr Scand Suppl 1985;318:79-88.
18. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
19. Juonala M, Viikari JS, Laitinen T, Marniemi J, Helenius H, Rönnemaa T, Raitakari OT. Interrelations between brachial endothelial function and carotid intima-media thickness in young adults: the cardiovascular risk in young Finns study. Circulation 2004;110:2918-2923.
20. Kivimäki M, Davey Smith G, Juonala M, Ferrie JE, Keltikangas-Järvinen L, Elovainio M, Pulkki-Råback L, Vahtera J, Leino M, Viikari JS, Raitakari OT. Socioeconomic position in childhood and adult cardiovascular risk factors, vascular structure and function: the Cardiovascular Risk in Young Finns study. Heart 2006;92:474-480.
21. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-419.
22. StatisticsFinland. Classification of Occupations. Helsinki: Statistics Finland; 1987.
23. Timpson NJ, Lawlor DA, Harbord RM, Gaunt TR, Day IN, Palmer LJ, Hattersley AT, Ebrahim S, Lowe GD, Rumley A, Davey Smith G. C-reactive protein and its role in metabolic syndrome: Mendelian randomisation study. Lancet 2005;366:1954-1959.
24. Davey Smith G, Lawlor DA, Harbord R, Timpson N, Rumley A, Lowe GD, Day IN, Ebrahim S. Association of C-reactive protein with blood pressure and hypertension. Life course confounding and Mendelian randomization tests of causality. Arterioscler Thromb Vasc Biol 2005;25:1051-1056.
25. Lawlor DA, Timpson N, Ebrahim S, Day IN, Davey Smith G. The association of oestrogen receptor alpha-haplotypes with cardiovascular risk factors in the British Women's Heart and Health Study. Eur Heart J 2006;27:1597- 1604.
26. Kivimäki M, Lawlor DA, Eklund C, Davey Smith G, Hurme M, Lehtimäki T, Viikari JSA, Raitakari OT. Mendelian randomization suggests no causal association between C-reactive protein and carotid intima-media thickness in the young Finns study. Arterioscler Thromb Vasc Biol 2007;27:978-979.
27. Sacerdote C, Guarrera S, Davey Smith G, Grioni S, Krogh V, Masala G, Mattiello A, Palli D, Panico S, Tumino R, Veglia F, Matullo G, Vineis P. Lactase persistence and bitter taste response: Instrumental variables and Mendelian randomization in epidemiologic studies of dietary factors and cancer risk. Am J Epidemiol 2007;166:576-581.
28. Keavney B, Danesh J, Parish S, Palmer A, Clark S, Youngman L, Delépine M, Lathrop M, Peto R, Collins R. Fibrinogen and coronary heart disease: test of causality by 'Mendelian randomization'. Int J Epidemiol 2006;35:935-943.
29. Casas JP, Shah T, Cooper J, Hawe E, McMahon AD, Gaffney D, Packard CJ, O'Reilly DS, Juhan-Vague I, Yudkin JS, Tremoli E, Margaglione M, Di Minno G, Hamsten A, Kooistra T, Stephens JW, Hurel SJ, Livingstone S, Colhoun HM, Miller GJ, Bautista LE, Meade T, Sattar N, Humphries SE, Hingorani AD. Insight into the nature of the CRP-coronary event association using Mendelian randomization. Int J Epidemiol 2006;35:922-931.
30. Casas JP, Bautista LE, Smeeth L, Sharma P, Hingorani AD. Homocysteine and stroke: evidence on a causal link from Mendelian randomisation. Lancet 2005;365:224-232.
31. Davey Smith G, Harbord R, Milton J, Ebrahim S, Sterne JA. Does elevated plasma fibrinogen increase the risk of coronary heart disease? Evidence from a meta-analysis of genetic association studies. Arterioscler Thromb Vasc Biol 2005;25:2228-2233.
32. Greenland S. An introduction to instrumental variables for epidemiologists. Int J Epidemiol 2000;29:722-729.
33. Stock JH, Wright JH, Yogo M. A survey of weak instruments and weak identification in generalized method of moments. J Bus Econ Stat 2002;20:518-529.
34. Staiger D, Stock JH. Instrumental variables regression with weak instruments. Econometrica J Econ Soc 1997;65:557-586.
35. Kivimäki M, Lawlor DA, Davey Smith G, Eklund C, Hurme M, Lehtimaki T, Viikari JSA, Raitakari OT. Variants in the CRP gene as a measure of lifelong differences in average C-reactive protein levels: the Cardiovascular Risk in Young Finns study, 1980-2001. Am J Epidemiol 2007;166:760-764.
36. Hillier TA, Pedula KL, Schmidt MM, Mullen JA, Charles MA, Pettitt DJ. Childhood obesity and metabolic imprinting: the ongoing effects of maternal hyperglycemia. Diabetes Care 2007;30:2287-2292.
37. Dabelea D, Hanson RL, Lindsay RS, Pettitt DJ, Imperatore G, Imperatore G, Gabir MM, Roumain J, Bennett PH, Knowler WC. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes 2000;49:2208-2211.
38. Kivimäki M, Lawlor DA, Davey Smith G, Elovainio M, Jokela M, Keltikangas-Järvinen L, Viikari JS, Raitakari OT. Substantial intergenerational increases in body mass index are not explained by the fetal overnutrition hypothesis: the Cardiovascular Risk in Young Finns study. Am J Clin Nutr 2007;86:1509-1514.
39. Davey Smith G, Lawlor DA, Harbord R, Timpson N, Day I, Ebrahim S. Clustered environments and randomized genes: a fundamental distinction between conventional and genetic epidemiology. PLoS Med 2007;4:e352.
40. Lee WL, Cheung AM, Cape D, Zinman B. Impact of diabetes on coronary artery disease in women and men: a meta-analysis of prospective studies. Diabetes Care 2000;23:962-968.
41. Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature 2006;444:875-880.
42. Katagiri H, Yamada T, Oka Y. Adiposity and cardiovascular disorders: disturbance of the regulatory system consisting of humoral and neuronal signals. Circ Res 2007;101:27-39.
43. Reusch JE, Draznin BB. Atherosclerosis in diabetes and insulin resistance. Diabetes Obes Metab 2007;9:455-463.
44. Freathy RM, Timpson NJ, Lawlor DA, Pouta A, Ben-Shlomo Y, Ruokonen A, Ebrahim S, Shields B, Zeggini E, Weedon MN, Lindgren CM, Lango H, Melzer D, Ferrucci L, Paolisso G, Neville MJ, Karpe F, Palmer CN, Morris AD, Elliott P, Jarvelin MR, Davey Smith G, McCarthy MI, Hattersley AT, Frayling TM. Common variation in the FTO gene alters diabetes-related metabolic traits to extent expected, given its effect on BMI. Diabetes 2008;57:1419-1426.
45. Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts), Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R, Dallongeville J, De Backer G, Ebrahim S, Gjelsvik B, Herrmann-Lingen C, Hoes A, Humphries S, Knapton M, Perk J, Priori SG, Pyorala K, Reiner Z, Ruilope L, Sans-Menendez S, Scholte op Reimer W, Weissberg P, Wood D, Yarnell J, Zamorano JL; Other experts who contributed to parts of the guidelines; Walma E, Fitzgerald T, Cooney MT, Dudina A;, European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG), Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Funck-Brentano C, Filippatos G, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Hellemans I, Altiner A, Bonora E, Durrington PN, Fagard R, Giampaoli S, Hemingway H, Hakansson J, Kjeldsen SE, Larsen ML, Mancia G, Manolis AJ, Orth-Gomer K, Pedersen T, Rayner M, Sammut M, Schneiderman N, Stalenhoef AF, Tokgözoglu L, Wiklund O, Zampelas A European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Eur Heart J 2007;28:2375-2414. Other experts who contributed to parts of the guidelines. European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG).
46. Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005;365:1389-1397.
47. Kim SH, Lee YM, Jee SH, Nam CM. Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Obes Res 2003;11:1116-1123.
48. Colquitt J, Clegg A, Loveman E, Royle P, Sidhu MK. Surgery for morbid obesity. Cochrane Database Syst Rev 2005; CD003641.