Korean J Physiol Pharmacol.  2021 Jan;25(1):1-14. 10.4196/kjpp.2021.25.1.1.

Genetic approaches toward understanding the individual variation in cardiac structure, function and responses to exercise training

Affiliations
  • 1Department of Sports Science, Seoul National University of Science and Technology, Seoul 01811, Korea

Abstract

Cardiovascular disease (CVD) accounts for approximately 30% of all deaths worldwide and its prevalence is constantly increasing despite advancements in medical treatments. Cardiac remodeling and dysfunction are independent risk factors for CVD. Recent studies have demonstrated that cardiac structure and function are genetically influenced, suggesting that understanding the genetic basis for cardiac structure and function could provide new insights into developing novel therapeutic targets for CVD. Regular exercise has long been considered a robust nontherapeutic method of treating or preventing CVD. However, recent studies also indicate that there is inter-individual variation in response to exercise. Nevertheless, the genetic basis for cardiac structure and function as well as their responses to exercise training have yet to be fully elucidated. Therefore, this review summarizes accumulated evidence supporting the genetic contribution to these traits, including findings from population-based studies and unbiased large genomic-scale studies in humans.

Keyword

Exercise; Heart; Multifactorial inheritance; Phenotype; Quantitative trait loci

Reference

1. Joseph P, Leong D, McKee M, Anand SS, Schwalm JD, Teo K, Mente A, Yusuf S. 2017; Reducing the global burden of cardiovascular disease, part 1: the epidemiology and risk factors. Circ Res. 121:677–694. DOI: 10.1161/CIRCRESAHA.117.308903. PMID: 28860318.
2. Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, Finkelstein EA, Hong Y, Johnston SC, Khera A, Lloyd-Jones DM, Nelson SA, Nichol G, Orenstein D, Wilson PW, Woo YJ. 2011; Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation. 123:933–944. DOI: 10.1161/CIR.0b013e31820a55f5. PMID: 21262990.
3. Wu A. 2018; Heart failure. Ann Intern Med. 168:ITC81–ITC96. DOI: 10.7326/AITC201806050. PMID: 29868816.
Article
4. Liu S, Li Y, Zeng X, Wang H, Yin P, Wang L, Liu Y, Liu J, Qi J, Ran S, Yang S, Zhou M. 2019; Burden of cardiovascular diseases in China, 1990-2016: findings from the 2016 Global Burden of Disease study. JAMA Cardiol. 4:342–352. DOI: 10.1001/jamacardio.2019.0295. PMID: 30865215. PMCID: PMC6484795.
5. Gu D, Gupta A, Muntner P, Hu S, Duan X, Chen J, Reynolds RF, Whelton PK, He J. 2005; Prevalence of cardiovascular disease risk factor clustering among the adult population of China: results from the International Collaborative Study of Cardiovascular Disease in Asia (InterAsia). Circulation. 112:658–665. DOI: 10.1161/CIRCULATIONAHA.104.515072. PMID: 16043645.
6. Lloyd-Jones DM, Nam BH, D'Agostino RB Sr, Levy D, Murabito JM, Wang TJ, Wilson PW, O'Donnell CJ. 2004; Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring. JAMA. 291:2204–2211. DOI: 10.1001/jama.291.18.2204. PMID: 15138242.
7. Warren HR, Evangelou E, Cabrera CP, Gao H, Ren M, Mifsud B, Ntalla I, Surendran P, Liu C, Cook JP, Kraja AT, Drenos F, Loh M, Verweij N, Marten J, Karaman I, Lepe MP, O'Reilly PF, Knight J, Snieder H, et al. 2017; Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Nat Genet. 49:403–415. DOI: 10.1038/ng.3768. PMID: 28135244. PMCID: PMC5972004.
Article
8. Nelson CP, Goel A, Butterworth AS, Kanoni S, Webb TR, Marouli E, Zeng L, Ntalla I, Lai FY, Hopewell JC, Giannakopoulou O, Jiang T, Hamby SE, Di Angelantonio E, Assimes TL, Bottinger EP, Chambers JC, Clarke R, Palmer CNA, Cubbon RM, et al. 2017; Association analyses based on false discovery rate implicate new loci for coronary artery disease. Nat Genet. 49:1385–1391. DOI: 10.1038/ng.3913. PMID: 28714975.
Article
9. Sivapalaratnam S, Motazacker MM, Maiwald S, Hovingh GK, Kastelein JJ, Levi M, Trip MD, Dallinga-Thie GM. 2011; Genome-wide association studies in atherosclerosis. Curr Atheroscler Rep. 13:225–232. DOI: 10.1007/s11883-011-0173-4. PMID: 21369780. PMCID: PMC3085784.
Article
10. Smith NL, Felix JF, Morrison AC, Demissie S, Glazer NL, Loehr LR, Cupples LA, Dehghan A, Lumley T, Rosamond WD, Lieb W, Rivadeneira F, Bis JC, Folsom AR, Benjamin E, Aulchenko YS, Haritunians T, Couper D, Murabito J, Wang YA, et al. 2010; Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry: a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium. Circ Cardiovasc Genet. 3:256–266. DOI: 10.1161/CIRCGENETICS.109.895763. PMID: 20445134. PMCID: PMC3025695.
11. Burchfield JS, Xie M, Hill JA. 2013; Pathological ventricular remodeling: mechanisms: part 1 of 2. Circulation. 128:388–400. DOI: 10.1161/CIRCULATIONAHA.113.001878. PMID: 23877061. PMCID: PMC3801217.
12. Tsao CW, Gona PN, Salton CJ, Chuang ML, Levy D, Manning WJ, O'Donnell CJ. 2015; Left ventricular structure and risk of cardiovascular events: a Framingham Heart Study cardiac magnetic resonance study. J Am Heart Assoc. 4:e002188. DOI: 10.1161/JAHA.115.002188. PMID: 26374295. PMCID: PMC4599505.
Article
13. Swan L, Birnie DH, Padmanabhan S, Inglis G, Connell JM, Hillis WS. 2003; The genetic determination of left ventricular mass in healthy adults. Eur Heart J. 24:577–582. DOI: 10.1016/S0195-668X(02)00524-9. PMID: 12643891.
Article
14. Arnett DK, Meyers KJ, Devereux RB, Tiwari HK, Gu CC, Vaughan LK, Perry RT, Patki A, Claas SA, Sun YV, Broeckel U, Kardia SL. 2011; Genetic variation in NCAM1 contributes to left ventricular wall thickness in hypertensive families. Circ Res. 108:279–283. DOI: 10.1161/CIRCRESAHA.110.239210. PMID: 21212386. PMCID: PMC3328104.
Article
15. Aung N, Vargas JD, Yang C, Cabrera CP, Warren HR, Fung K, Tzanis E, Barnes MR, Rotter JI, Taylor KD, Manichaikul AW, Lima JAC, Bluemke DA, Piechnik SK, Neubauer S, Munroe PB, Petersen SE. 2019; Genome-wide analysis of left ventricular image-derived phenotypes identifies fourteen loci associated with cardiac morphogenesis and heart failure development. Circulation. 140:1318–1330. DOI: 10.1161/CIRCULATIONAHA.119.041161. PMID: 31554410. PMCID: PMC6791514.
Article
16. Kanai M, Akiyama M, Takahashi A, Matoba N, Momozawa Y, Ikeda M, Iwata N, Ikegawa S, Hirata M, Matsuda K, Kubo M, Okada Y, Kamatani Y. 2018; Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases. Nat Genet. 50:390–400. DOI: 10.1038/s41588-018-0047-6. PMID: 29403010.
Article
17. Do AN, Zhao W, Baldridge AS, Raffield LM, Wiggins KL, Shah SJ, Aslibekyan S, Tiwari HK, Limdi N, Zhi D, Sitlani CM, Taylor KD, Psaty BM, Sotoodehnia N, Brody JA, Rasmussen-Torvik LJ, Lloyd-Jones D, Lange LA, Wilson JG, Smith JA, et al. 2019; Genome-wide meta-analysis of SNP and antihypertensive medication interactions on left ventricular traits in African Americans. Mol Genet Genomic Med. 7:e00788. DOI: 10.1002/mgg3.788. PMID: 31407531. PMCID: PMC6785453.
Article
18. Wild PS, Felix JF, Schillert A, Teumer A, Chen MH, Leening MJG, Völker U, Großmann V, Brody JA, Irvin MR, Shah SJ, Pramana S, Lieb W, Schmidt R, Stanton AV, Malzahn D, Smith AV, Sundström J, Minelli C, Ruggiero D, et al. 2017; Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function. J Clin Invest. 127:1798–1812. DOI: 10.1172/JCI84840. PMID: 28394258. PMCID: PMC5409098.
Article
19. Fox ER, Musani SK, Barbalic M, Lin H, Yu B, Ogunyankin KO, Smith NL, Kutlar A, Glazer NL, Post WS, Paltoo DN, Dries DL, Farlow DN, Duarte CW, Kardia SL, Meyers KJ, Sun YV, Arnett DK, Patki AA, Sha J, et al. 2013; Genome-wide association study of cardiac structure and systolic function in African Americans: the Candidate Gene Association Resource (CARe) study. Circ Cardiovasc Genet. 6:37–46. DOI: 10.1161/CIRCGENETICS.111.962365. PMID: 23275298. PMCID: PMC3591479.
20. Dueker ND, Guo S, Beecham A, Wang L, Blanton SH, Di Tullio MR, Rundek T, Sacco RL. 2018; Sequencing of linkage region on chromosome 12p11 identifies PKP2 as a candidate gene for left ventricular mass in Dominican families. G3 (Bethesda). 8:659–668. DOI: 10.1534/g3.117.300358. PMID: 29288195. PMCID: PMC5919734.
21. Vasan RS, Glazer NL, Felix JF, Lieb W, Wild PS, Felix SB, Watzinger N, Larson MG, Smith NL, Dehghan A, Grosshennig A, Schillert A, Teumer A, Schmidt R, Kathiresan S, Lumley T, Aulchenko YS, König IR, Zeller T, Homuth G, et al. 2009; Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data. JAMA. 302:168–178. DOI: 10.1001/jama.2009.978-a. PMID: 19584346. PMCID: PMC2975567.
22. Kathiresan S, ivastava D Sr. 2012; Genetics of human cardiovascular disease. Cell. 148:1242–1257. DOI: 10.1016/j.cell.2012.03.001. PMID: 22424232. PMCID: PMC3319439.
Article
23. Kim MS, Patel KP, Teng AK, Berens AJ, Lachance J. 2018; Genetic disease risks can be misestimated across global populations. Genome Biol. 19:179. DOI: 10.1186/s13059-018-1561-7. PMID: 30424772. PMCID: PMC6234640.
Article
24. Zadro JR, Shirley D, Andrade TB, Scurrah KJ, Bauman A, Ferreira PH. 2017; The beneficial effects of physical activity: is it down to your genes? A systematic review and meta-analysis of twin and family studies. Sports Med Open. 3:4. DOI: 10.1186/s40798-016-0073-9. PMID: 28074345. PMCID: PMC5225201.
Article
25. Galton F. 2012; The history of twins, as a criterion of the relative powers of nature and nurture (1,2). Int J Epidemiol. 41:905–911. DOI: 10.1093/ije/dys097. PMID: 22933639.
26. Boomsma D, Busjahn A, Peltonen L. 2002; Classical twin studies and beyond. Nat Rev Genet. 3:872–882. DOI: 10.1038/nrg932. PMID: 12415317.
Article
27. Badzioch MD, Igo RP Jr, Gagnon F, Brunzell JD, Krauss RM, Motulsky AG, Wijsman EM, Jarvik GP. 2004; Low-density lipoprotein particle size loci in familial combined hyperlipidemia: evidence for multiple loci from a genome scan. Arterioscler Thromb Vasc Biol. 24:1942–1950. DOI: 10.1161/01.ATV.0000143499.09575.93. PMID: 15331429.
28. Borecki IB, Province MA. 2008; Genetic and genomic discovery using family studies. Circulation. 118:1057–1063. DOI: 10.1161/CIRCULATIONAHA.107.714592. PMID: 18765388.
Article
29. Zhao LP, Hsu L, Davidov O, Potter J, Elston RC, Prentice RL. 1997; Population-based family study designs: an interdisciplinary research framework for genetic epidemiology. Genet Epidemiol. 14:365–388. DOI: 10.1002/(SICI)1098-2272(1997)14:4<365::AID-GEPI3>3.0.CO;2-2. PMID: 9271710.
Article
30. Wang Y, Wang JG. 2019; Genome-wide association studies of hypertension and several other cardiovascular diseases. Pulse (Basel). 6:169–186. DOI: 10.1159/000496150. PMID: 31049317. PMCID: PMC6489084.
Article
31. Stranger BE, Stahl EA, Raj T. 2011; Progress and promise of genome-wide association studies for human complex trait genetics. Genetics. 187:367–383. DOI: 10.1534/genetics.110.120907. PMID: 21115973. PMCID: PMC3030483.
Article
32. Kessler T, Vilne B, Schunkert H. 2016; The impact of genome-wide association studies on the pathophysiology and therapy of cardiovascular disease. EMBO Mol Med. 8:688–701. DOI: 10.15252/emmm.201506174. PMID: 27189168. PMCID: PMC4931285.
33. Fiuza-Luces C, Santos-Lozano A, Joyner M, Carrera-Bastos P, Picazo O, Zugaza JL, Izquierdo M, Ruilope LM, Lucia A. 2018; Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors. Nat Rev Cardiol. 15:731–743. DOI: 10.1038/s41569-018-0065-1. PMID: 30115967.
Article
34. Church TS, Earnest CP, Skinner JS, Blair SN. 2007; Effects of different doses of physical activity on cardiorespiratory fitness among sedentary, overweight or obese postmenopausal women with elevated blood pressure: a randomized controlled trial. JAMA. 297:2081–2091. DOI: 10.1001/jama.297.19.2081. PMID: 17507344.
35. Jeong SW, Kim SH, Kang SH, Kim HJ, Yoon CH, Youn TJ, Chae IH. 2019; Mortality reduction with physical activity in patients with and without cardiovascular disease. Eur Heart J. 40:3547–3555. DOI: 10.1093/eurheartj/ehz564. PMID: 31504416. PMCID: PMC6855138.
Article
36. Nystoriak MA, Bhatnagar A. 2018; Cardiovascular effects and benefits of exercise. Front Cardiovasc Med. 5:135. DOI: 10.3389/fcvm.2018.00135. PMID: 30324108. PMCID: PMC6172294.
Article
37. Lavie CJ, Arena R, Swift DL, Johannsen NM, Sui X, Lee DC, Earnest CP, Church TS, O'Keefe JH, Milani RV, Blair SN. 2015; Exercise and the cardiovascular system: clinical science and cardiovascular outcomes. Circ Res. 117:207–219. DOI: 10.1161/CIRCRESAHA.117.305205. PMID: 26139859. PMCID: PMC4493772.
38. Arbab-Zadeh A, Perhonen M, Howden E, Peshock RM, Zhang R, Adams-Huet B, Haykowsky MJ, Levine BD. 2014; Cardiac remodeling in response to 1 year of intensive endurance training. Circulation. 130:2152–2161. DOI: 10.1161/CIRCULATIONAHA.114.010775. PMID: 25281664. PMCID: PMC5698012.
Article
39. Kim SK, Massett MP. 2016; Genetic regulation of endothelial vasomotor function. Front Physiol. 7:571. DOI: 10.3389/fphys.2016.00571. PMID: 27932996. PMCID: PMC5122706.
Article
40. Álvarez C, Ramírez-Campillo R, Ramírez-Vélez R, Izquierdo M. 2017; Effects and prevalence of nonresponders after 12 weeks of high-intensity interval or resistance training in women with insulin resistance: a randomized trial. J Appl Physiol. 122:985–996. DOI: 10.1152/japplphysiol.01037.2016. PMID: 28153946.
Article
41. Bonafiglia JT, Rotundo MP, Whittall JP, Scribbans TD, Graham RB, Gurd BJ. 2016; Inter-individual variability in the adaptive responses to endurance and sprint interval training: a randomized crossover study. PLoS One. 11:e0167790. DOI: 10.1371/journal.pone.0167790. PMID: 27936084. PMCID: PMC5147982.
Article
42. Bouchard C, Rankinen T. 2001; Individual differences in response to regular physical activity. Med Sci Sports Exerc. 33(6 Suppl):S446–S451. discussion S452–S453. DOI: 10.1097/00005768-200106001-00013. PMID: 11427769.
Article
43. Williams CJ, Williams MG, Eynon N, Ashton KJ, Little JP, Wisloff U, Coombes JS. 2017; Genes to predict VO2max trainability: a systematic review. BMC Genomics. 18(Suppl 8):831. DOI: 10.1186/s12864-017-4192-6. PMID: 29143670. PMCID: PMC5688475.
Article
44. Bouchard C, Blair SN, Church TS, Earnest CP, Hagberg JM, Häkkinen K, Jenkins NT, Karavirta L, Kraus WE, Leon AS, Rao DC, Sarzynski MA, Skinner JS, Slentz CA, Rankinen T. 2012; Adverse metabolic response to regular exercise: is it a rare or common occurrence? PLoS One. 7:e37887. DOI: 10.1371/journal.pone.0037887. PMID: 22666405. PMCID: PMC3364277.
Article
45. Bouchard C, Rankinen T, Timmons JA. 2011; Genomics and genetics in the biology of adaptation to exercise. Compr Physiol. 1:1603–1648. DOI: 10.1002/cphy.c100059. PMID: 23733655. PMCID: PMC3938186.
Article
46. Ross R, Goodpaster BH, Koch LG, Sarzynski MA, Kohrt WM, Johannsen NM, Skinner JS, Castro A, Irving BA, Noland RC, Sparks LM, Spielmann G, Day AG, Pitsch W, Hopkins WG, Bouchard C. 2019; Precision exercise medicine: understanding exercise response variability. Br J Sports Med. 53:1141–1153. DOI: 10.1136/bjsports-2018-100328. PMID: 30862704. PMCID: PMC6818669.
Article
47. Bouchard C, Leon AS, Rao DC, Skinner JS, Wilmore JH, Gagnon J. 1995; The HERITAGE family study. Aims, design, and measurement protocol. Med Sci Sports Exerc. 27:721–729. DOI: 10.1249/00005768-199505000-00015. PMID: 7674877.
48. Adams TD, Yanowitz FG, Fisher AG, Ridges JD, Nelson AG, Hagan AD, Williams RR, Hunt SC. 1985; Heritability of cardiac size: an echocardiographic and electrocardiographic study of monozygotic and dizygotic twins. Circulation. 71:39–44. DOI: 10.1161/01.CIR.71.1.39. PMID: 4038369.
Article
49. Fox ER, Klos KL, Penman AD, Blair GJ, Blossom BD, Arnett D, Devereux RB, Samdarshi T, Boerwinkle E, Mosley TH Jr. 2010; Heritability and genetic linkage of left ventricular mass, systolic and diastolic function in hypertensive African Americans (from the GENOA Study). Am J Hypertens. 23:870–875. DOI: 10.1038/ajh.2010.67. PMID: 20448532. PMCID: PMC3292847.
Article
50. Garner C, Lecomte E, Visvikis S, Abergel E, Lathrop M, Soubrier F. 2000; Genetic and environmental influences on left ventricular mass. A family study. Hypertension. 36:740–746. DOI: 10.1161/01.HYP.36.5.740. PMID: 11082137.
51. Juo SH, Di Tullio MR, Lin HF, Rundek T, Boden-Albala B, Homma S, Sacco RL. 2005; Heritability of left ventricular mass and other morphologic variables in Caribbean Hispanic subjects: the Northern Manhattan Family Study. J Am Coll Cardiol. 46:735–737. DOI: 10.1016/j.jacc.2005.05.025. PMID: 16098447. PMCID: PMC2692931.
52. Lam CS, Liu X, Yang Q, Larson MG, Pencina MJ, Aragam J, Redfield MM, Benjamin EJ, Vasan RS. 2010; Familial aggregation of left ventricular geometry and association with parental heart failure: the Framingham Heart Study. Circ Cardiovasc Genet. 3:492–498. DOI: 10.1161/CIRCGENETICS.110.941088. PMID: 20884845. PMCID: PMC3785074.
53. Post WS, Larson MG, Myers RH, Galderisi M, Levy D. 1997; Heritability of left ventricular mass: the Framingham Heart Study. Hypertension. 30:1025–1028. DOI: 10.1161/01.HYP.30.5.1025. PMID: 9369250.
54. Bella JN, MacCluer JW, Roman MJ, Almasy L, North KE, Best LG, Lee ET, Fabsitz RR, Howard BV, Devereux RB. 2004; Heritability of left ventricular dimensions and mass in American Indians: the Strong Heart Study. J Hypertens. 22:281–286. DOI: 10.1097/00004872-200402000-00011. PMID: 15076185.
55. Bielen E, Fagard R, Amery A. 1991; The inheritance of left ventricular structure and function assessed by imaging and Doppler echocardiography. Am Heart J. 121(6 Pt 1):1743–1749. DOI: 10.1016/0002-8703(91)90021-9. PMID: 2035387.
Article
56. Hannukainen JC, Kujala UM, Toikka J, Heinonen OJ, Kapanen J, Vahlberg T, Kaprio J, Kalliokoski KK. 2005; Cardiac structure and function in monozygotic twin pairs discordant for physical fitness. J Appl Physiol. 99:535–541. DOI: 10.1152/japplphysiol.00107.2005. PMID: 15817727.
Article
57. Verhaaren HA, Schieken RM, Mosteller M, Hewitt JK, Eaves LJ, Nance WE. 1991; Bivariate genetic analysis of left ventricular mass and weight in pubertal twins (the Medical College of Virginia twin study). Am J Cardiol. 68:661–668. DOI: 10.1016/0002-9149(91)90361-N. PMID: 1877484.
Article
58. Busjahn CA, Schulz-Menger J, Abdel-Aty H, Rudolph A, Jordan J, Luft FC, Busjahn A. 2009; Heritability of left ventricular and papillary muscle heart size: a twin study with cardiac magnetic resonance imaging. Eur Heart J. 30:1643–1647. DOI: 10.1093/eurheartj/ehp142. PMID: 19406865.
Article
59. Kapuku GK, Ge D, Vemulapalli S, Harshfield GA, Treiber FA, Snieder H. 2008; Change of genetic determinants of left ventricular structure in adolescence: longitudinal evidence from the Georgia cardiovascular twin study. Am J Hypertens. 21:799–805. DOI: 10.1038/ajh.2008.178. PMID: 18443564. PMCID: PMC3857089.
Article
60. Noh HM, Lee SC, Park SW, Sung J, Song YM. 2015; Genetic influence on left ventricular structure and function: a Korean twin and family study. Twin Res Hum Genet. 18:281–289. DOI: 10.1017/thg.2015.18. PMID: 25871282.
Article
61. Fagard R, Van Den Broeke C, Bielen E, Amery A. 1987; Maximum oxygen uptake and cardiac size and function in twins. Am J Cardiol. 60:1362–1367. DOI: 10.1016/0002-9149(87)90620-5. PMID: 3687786.
Article
62. Bielen E, Fagard R, Amery A. 1990; Inheritance of heart structure and physical exercise capacity: a study of left ventricular structure and exercise capacity in 7-year-old twins. Eur Heart J. 11:7–16. DOI: 10.1093/oxfordjournals.eurheartj.a059595. PMID: 2307165.
Article
63. Bielen EC, Fagard RH, Amery AK. 1991; Inheritance of acute cardiac changes during bicycle exercise: an echocardiographic study in twins. Med Sci Sports Exerc. 23:1254–1259. DOI: 10.1249/00005768-199111000-00009. PMID: 1766340.
64. Vasan RS, Larson MG, Aragam J, Wang TJ, Mitchell GF, Kathiresan S, Newton-Cheh C, Vita JA, Keyes MJ, O'Donnell CJ, Levy D, Benjamin EJ. 2007; Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study. BMC Med Genet. 8(Suppl 1):S2. DOI: 10.1186/1471-2350-8-S1-S2. PMID: 17903301. PMCID: PMC1995617.
Article
65. Palatini P, Krause L, Amerena J, Nesbitt S, Majahalme S, Tikhonoff V, Valentini M, Julius S. 2001; Genetic contribution to the variance in left ventricular mass: the Tecumseh Offspring Study. J Hypertens. 19:1217–1222. DOI: 10.1097/00004872-200107000-00006. PMID: 11446711.
Article
66. An P, Rice T, Gagnon J, Leon AS, Skinner JS, Bouchard C, Rao DC, Wilmore JH. 2000; Familial aggregation of stroke volume and cardiac output during submaximal exercise: the HERITAGE Family Study. Int J Sports Med. 21:566–572. DOI: 10.1055/s-2000-12983. PMID: 11156276.
Article
67. Schunkert H, Bröckel U, Hengstenberg C, Luchner A, Muscholl MW, Kurzidim K, Kuch B, Döring A, Riegger GA, Hense HW. 1999; Familial predisposition of left ventricular hypertrophy. J Am Coll Cardiol. 33:1685–1691. DOI: 10.1016/S0735-1097(99)00050-9. PMID: 10334443.
Article
68. Arnett DK, Hong Y, Bella JN, Oberman A, Kitzman DW, Hopkins PN, Rao DC, Devereux RB. 2001; Sibling correlation of left ventricular mass and geometry in hypertensive African Americans and whites: the HyperGEN study. Hypertension Genetic Epidemiology Network. Am J Hypertens. 14:1226–1230. DOI: 10.1016/S0895-7061(01)02200-2. PMID: 11775131.
69. Chien KL, Hsu HC, Su TC, Chen MF, Lee YT. 2006; Heritability and major gene effects on left ventricular mass in the Chinese population: a family study. BMC Cardiovasc Disord. 6:37. DOI: 10.1186/1471-2261-6-37. PMID: 16945138. PMCID: PMC1579230.
Article
70. Peterson VR, Norton GR, Redelinghuys M, Libhaber CD, Maseko MJ, Majane OH, Brooksbank R, Woodiwiss AJ. 2015; Intrafamilial aggregation and heritability of left ventricular geometric remodeling is independent of cardiac mass in families of African ancestry. Am J Hypertens. 28:657–663. DOI: 10.1093/ajh/hpu202. PMID: 25376640. PMCID: PMC4462652.
Article
71. Balding DJ. 2006; A tutorial on statistical methods for population association studies. Nat Rev Genet. 7:781–791. DOI: 10.1038/nrg1916. PMID: 16983374.
Article
72. Arnett DK, Li N, Tang W, Rao DC, Devereux RB, Claas SA, Kraemer R, Broeckel U. 2009; Genome-wide association study identifies single-nucleotide polymorphism in KCNB1 associated with left ventricular mass in humans: the HyperGEN Study. BMC Med Genet. 10:43. DOI: 10.1186/1471-2350-10-43. PMID: 19454037. PMCID: PMC2692849.
Article
73. Tang W, Arnett DK, Devereux RB, Panagiotou D, Province MA, Miller MB, de Simone G, Gu C, Ferrell RE. 2005; Identification of a novel 5-base pair deletion in calcineurin B (PPP3R1) promoter region and its association with left ventricular hypertrophy. Am Heart J. 150:845–851. DOI: 10.1016/j.ahj.2004.12.004. PMID: 16209992.
Article
74. Wang L, Beecham A, Di Tullio MR, Slifer S, Blanton SH, Rundek T, Sacco RL. 2009; Novel quantitative trait locus is mapped to chromosome 12p11 for left ventricular mass in Dominican families: the Family Study of Stroke Risk and Carotid Atherosclerosis. BMC Med Genet. 10:74. DOI: 10.1186/1471-2350-10-74. PMID: 19627612. PMCID: PMC2724377.
Article
75. Parsa A, Chang YP, Kelly RJ, Corretti MC, Ryan KA, Robinson SW, Gottlieb SS, Kardia SL, Shuldiner AR, Liggett SB. 2011; Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality. Clin Transl Sci. 4:17–23. DOI: 10.1111/j.1752-8062.2010.00251.x. PMID: 21348951. PMCID: PMC4373555.
Article
76. Bild DE, Bluemke DA, Burke GL, Detrano R, Diez Roux AV, Folsom AR, Greenland P, Jacob DR Jr, Kronmal R, Liu K, Nelson JC, O'Leary D, Saad MF, Shea S, Szklo M, Tracy RP. 2002; Multi-Ethnic Study of Atherosclerosis: objectives and design. Am J Epidemiol. 156:871–881. DOI: 10.1093/aje/kwf113. PMID: 12397006.
Article
77. Rankinen T, An P, Pérusse L, Rice T, Chagnon YC, Gagnon J, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. 2002; Genome-wide linkage scan for exercise stroke volume and cardiac output in the HERITAGE Family Study. Physiol Genomics. 10:57–62. DOI: 10.1152/physiolgenomics.00043.2002. PMID: 12181362.
Article
78. Vega RB, Konhilas JP, Kelly DP, Leinwand LA. 2017; Molecular mechanisms underlying cardiac adaptation to exercise. Cell Metab. 25:1012–1026. DOI: 10.1016/j.cmet.2017.04.025. PMID: 28467921. PMCID: PMC5512429.
Article
79. Eynon N, Ruiz JR, Oliveira J, Duarte JA, Birk R, Lucia A. 2011; Genes and elite athletes: a roadmap for future research. J Physiol (Lond). 589(Pt 13):3063–3070. DOI: 10.1113/jphysiol.2011.207035. PMID: 21540342. PMCID: PMC3145924.
Article
80. Bray MS, Hagberg JM, Pérusse L, Rankinen T, Roth SM, Wolfarth B, Bouchard C. 2009; The human gene map for performance and health-related fitness phenotypes: the 2006-2007 update. Med Sci Sports Exerc. 41:35–73. DOI: 10.1249/MSS.0b013e3181844179. PMID: 19123262.
81. Bouchard C, Sarzynski MA, Rice TK, Kraus WE, Church TS, Sung YJ, Rao DC, Rankinen T. 2011; Genomic predictors of the maximal O₂ uptake response to standardized exercise training programs. J Appl Physiol. 110:1160–1170. DOI: 10.1152/japplphysiol.00973.2010. PMID: 21183627. PMCID: PMC3098655.
82. Kagamimori S, Robson JM, Heywood C, Cotes JE. 1984; Genetic and environmental determinants of the cardio-respiratory response to submaximal exercise--a six-year follow-up study of twins. Ann Hum Biol. 11:29–38. DOI: 10.1080/03014468400006861. PMID: 6538396.
Article
83. Mutikainen S, Perhonen M, Alén M, Leskinen T, Karjalainen J, Rantanen T, Kaprio J, Kujala UM. 2009; Effects of long-term physical activity on cardiac structure and function: a twin study. J Sports Sci Med. 8:533–542. PMID: 24149594. PMCID: PMC3761543.
84. Wilmore JH, Stanforth PR, Gagnon J, Rice T, Mandel S, Leon AS, Rao DC, Skinner JS, Bouchard C. 2001; Cardiac output and stroke volume changes with endurance training: the HERITAGE Family Study. Med Sci Sports Exerc. 33:99–106. DOI: 10.1097/00005768-200101000-00016. PMID: 11194119.
Article
85. Argyropoulos G, Stütz AM, Ilnytska O, Rice T, Teran-Garcia M, Rao DC, Bouchard C, Rankinen T. 2009; KIF5B gene sequence variation and response of cardiac stroke volume to regular exercise. Physiol Genomics. 36:79–88. DOI: 10.1152/physiolgenomics.00003.2008. PMID: 18984674. PMCID: PMC2636926.
Article
86. Rankinen T, Rice T, Boudreau A, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. 2003; Titin is a candidate gene for stroke volume response to endurance training: the HERITAGE Family Study. Physiol Genomics. 15:27–33. DOI: 10.1152/physiolgenomics.00147.2002. PMID: 12865504.
Article
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