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The Identification of Hereditary and Environmental Determinants of Frailty in a Cohort of UK Twins

  • Aideen C. M. Young (a1), Karen Glaser (a1), Timothy D. Spector (a2) and Claire J. Steves (a2)
Abstract

Our study examines the contribution of genetic and environmental factors (both shared and unique) to frailty, measured using the Rockwood Frailty Index (FI) in a sample of twins from the St Thomas’ UK Adult Twin Registry. The FI was based on 39 items of potential health deficit. Study participants were 3,375 volunteer adult twins (840 monozygotic and 802 dizygotic twin-pairs) 40.0–84.5 years old. First, we used structural equation modeling to estimate the relative contribution of genetics and of the shared and unique environment to variance in FI adjusted for age. In a second analysis, multiple linear regression was used to examine variance in FI as a function of father's occupational class (a component of shared environment and a measure of childhood socioeconomic status [SES]), adjusting for age, birth weight, marital status, and health behaviors (smoking, alcohol consumption, and physical activity). Statistical analyses were conducted using IBM SPSS® Version 22 software and Mx open source software. Findings showed that 45% (95% confidence intervals [CIs] 30–53%) of the inter-individual variation in FI was heritable and 52% (95% CIs 47–57%) was due to the individual's unique environment. Multiple linear regression also showed a small but statistically significant inverse association between father's occupational class and FI, mediated by one's own educational attainment and birth weight. Our results indicate that frailty is both genetically and environmentally determined. Thus, its prevention and management call for a multifaceted approach that includes addressing deleterious environmental factors, some of which, like childhood SES, may act across the life course.

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Corresponding author
address for correspondence: Aideen C. M. Young, Institute of Gerontology, Department of Global Health and Social Medicine, King's College London, London, UK. E-mail: aideen.young@kcl.ac.uk
References
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Adler, N. E., & Stewart, J. (2010). Health disparities across the lifespan: Meaning, methods, and mechanisms. Annals of the New York Academy of Sciences, 1186, 523.
Almeida, O. P., Norman, P. E., Van Bockxmeer, F. M., Hankey, G. J., & Flicker, L. (2012). CRP 1846G>A polymorphism increases risk of frailty. Maturitas, 71, 261266.
Alvarado, B. E., Zunzunegui, M. V., Beland, F., & Bamvita, J. M. (2008). Life course social and health conditions linked to frailty in Latin American older men and women. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 63, 13991406.
Andrew, M. K., Mitnitski, A. B., & Rockwood, K. (2008). Social vulnerability, frailty and mortality in elderly people. PLoS One, 3, e2232.
Andrew, T., Hart, D. J., Snieder, H., de Lange, M., Spector, T. D., & MacGregor, A. J. (2001). Are twins and singletons comparable? A study of disease-related and lifestyle characteristics in adult women. Twin Research, 4, 464477.
Bagot, R. C., & Meaney, M. J. (2010). Epigenetics and the biological basis of gene x environment interactions. Journal of the American Academy of Child and Adolescent Psychiatry, 49, 752771.
Batty, G. D., Lawlor, D. A., Macintyre, S., Clark, H., & Leon, D. A. (2005). Accuracy of adults' recall of childhood social class: Findings from the Aberdeen children of the 1950s study. Journal of Epidemiology and Community Health, 59, 898903.
Bellizzi, D., D'Aquila, P., Montesanto, A., Corsonello, A., Mari, V., Mazzei, B., . . . Passarino, G. (2012). Global DNA methylation in old subjects is correlated with frailty. Age (Dordrecht), 34, 169179.
Bengtsson, T., & Lindstrom, M. (2000). Childhood misery and disease in later life: The effects on mortality in old age of hazards experienced in early life, southern Sweden, 1760–1894. Population Studies (Cambridge), 54, 263277.
Bergman, H., Ferrucci, L., Guralnik, J., Hogan, D. B., Hummel, S., Karunananthan, S., & Wolfson, C. (2007). Frailty: An emerging research and clinical paradigm — issues and controversies. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 62, 731737.
Boomsma, D., Busjahn, A., & Peltonen, L. (2002). Classical twin studies and beyond. Nature Reviews Genetics, 3, 872882.
Breitling, L. P., Saum, K. U., Perna, L., Schöttker, B., Holleczek, B., & Brenner, H. (2016). Frailty is associated with the epigenetic clock but not with telomere length in a German cohort. Clinical Epigenetics, 8, 21.
Bruder, C. E., Piotrowski, A., Gijsbers, A. A., Andersson, R., Erickson, S., Diaz de Stahl, T., . . . Dumanski, J. P. (2008). Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. American Journal of Human Genetics, 82, 763771.
Burdge, G. C., Slater-Jefferies, J., Torrens, C., Phillips, E. S., Hanson, M. A., & Lillycrop, K. A. (2007). Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations. British Journal of Nutrition, 97, 435439.
Cesari, M., Marzetti, E., Thiem, U., Perez-Zepeda, M. U., Abellan Van Kan, G., Landi, F., . . . Bernabei, R. (2016). The geriatric management of frailty as paradigm of ‘The end of the disease era’. European Journal of Internal Medicine, 31, 1114.
Christensen, K., Johnson, T. E., & Vaupel, J. W. (2006). The quest for genetic determinants of human longevity: Challenges and insights. Nature Reviews Genetics, 7, 436448.
Clegg, A., Young, J., Iliffe, S., Rikkert, M. O., & Rockwood, K. (2013). Frailty in elderly people. Lancet, 381, 752762.
Collerton, J., Gautrey, H. E., van Otterdijk, S. D., Davies, K., Martin-Ruiz, C., von Zglinicki, T., . . . Strathdee, G. (2014). Acquisition of aberrant DNA methylation is associated with frailty in the very old: Findings from the Newcastle 85+ study. Biogerontology, 15, 317328.
Cramm, J. M., & Nieboer, A. P. (2013). Relationships between frailty, neighborhood security, social cohesion and sense of belonging among community-dwelling older people. Geriatrics and Gerontology International, 13, 759763.
Crimmins, E. M., & Cambois, E. (2003). Social inequalities in life expectancy. In Robine, J. M., Jagger, C., Mathers, C. D., Crimmins, E. M. & Suzman, R. M. (Eds.), Determining health expectancies (pp. 111126). Chichester, UK: John Wiley and Sons.
Dato, S., Montesanto, A., Lagani, V., Jeune, B., Christensen, K., & Passarino, G. (2012). Frailty phenotypes in the elderly based on cluster analysis: A longitudinal study of two Danish cohorts. Evidence for a genetic influence on frailty. Age (Dordrecht), 34, 571582.
Derks, E. M., Dolan, C. V., & Boomsma, D. I. (2006). A test of the equal environment assumption (EEA) in multivariate twin studies. Twin Research and Human Genetics, 9, 403411.
Etman, A., Kamphuis, C. B., van der Cammen, T. J., Burdorf, A., & van Lenthe, F. J. (2015). Do lifestyle, health and social participation mediate educational inequalities in frailty worsening? European Journal of Public Health, 25, 345350.
Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., . . . Esteller, M. (2005). Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences of the United States of America, 102, 1060410609.
Freudenstein, U., Arthur, A. J., Matthews, R. J., & Jagger, C. (2001). Community surveys of late-life depression: Who are the non-responders? Age and Ageing, 30, 517521.
Fried, L. P., & Walston, J. M. (2003). Frailty and failure to thrive. In Hazzard, W. R., Blass, J. P., Halter, J. & Ouslander, J. (Eds.), Principles of geriatric medicine and gerontology (5th ed., pp. 13871402). New York: McGraw-Hill Professional.
Gladman, J. R., Conroy, S. P., Ranhoff, A. H., & Gordon, A. L. (2016). New horizons in the implementation and research of comprehensive geriatric assessment: Knowing, doing and the ‘know-do’ gap. Age and Ageing, 45, 194200.
Goldberg, M., Chastang, J. F., Leclerc, A., Zins, M., Bonenfant, S., Bugel, I., . . . Imbernon, E. (2001). Socioeconomic, demographic, occupational, and health factors associated with participation in a long-term epidemiologic survey: A prospective study of the French GAZEL cohort and its target population. American Journal of Epidemiology, 154, 373384.
Hayward, M. D., & Gorman, B. K. (2004). The long arm of childhood: The influence of early-life social conditions on men's mortality. Demography, 41, 87107.
Herr, M., Robine, J. M., Aegerter, P., Arvieu, J. J., & Ankri, J. (2015). Contribution of socioeconomic position over life to frailty differences in old age: Comparison of life-course models in a French sample of 2350 old people. Annals of Epidemiology, 25, 674680.
Hoeymans, N., Feskens, E. J., Van Den Bos, G. A., & Kromhout, D. (1998). Non-response bias in a study of cardiovascular diseases, functional status and self-rated health among elderly men. Age and Ageing, 27, 3540.
Hoogendijk, E. O., van Hout, H. P., Heymans, M. W., van der Horst, H. E., Frijters, D. H., Broese van Groenou, M. I., . . . Huisman, M. (2014). Explaining the association between educational level and frailty in older adults: Results from a 13-year longitudinal study in the Netherlands. Annals of Epidemiology, 24, 538544.
Hubbard, R. E., Searle, S. D., Mitnitski, A., & Rockwood, K. (2009). Effect of smoking on the accumulation of deficits, frailty and survival in older adults: A secondary analysis from the Canadian study of health and aging. The Journal of Nutrition, Health and Aging, 13, 468472.
Kendler, K. S., Neale, M. C., Kessler, R. C., Heath, A. C., & Eaves, L. J. (1993). A test of the equal-environment assumption in twin studies of psychiatric illness. Behavior Genetics, 23, 2127.
Krieger, N., Okamoto, A., & Selby, J. V. (1998). Adult female twins’ recall of childhood social class and father's education: A validation study for public health research. American Journal of Epidemiology, 147, 704708.
Lang, I. A., Hubbard, R. E., Andrew, M. K., Llewllyn, D. J., Melzer, D., & Rockwood, K. (2009). Neighborhood deprivation, individual socioeconomic status, and frailty in older adults. Journal of the American Geriatric Society, 57, 17761780.
Leigh, J. P., & Fries, J. F. (2002). Frailty and education in the Hispanic health and nutrition examination survey. Journal of Health Care for the Poor and Underserved, 13, 112127.
Marioni, R. E., Shah, S., McRae, A. F., Ritchie, S. J., Muniz-Terrera, G., Harris, S. E., . . . Deary, I. J. (2015). The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936. International Journal of Epidemiology, 44, 13881396.
Marshall, A., Nazroo, J., Tampubolon, G., & Vanhoutte, B. (2015). Cohort differences in the levels and trajectories of frailty among older people in England. Journal of Epidemiology and Community Health, 69, 316321.
Miles, T. P. (1997). Population-based, genetically informative sample for studies of physical frailty and aging: Black elderly twin study. Human Biology, 69, 107120.
Mitnitski, A. B., Song, X., & Rockwood, K. (2004). The estimation of relative fitness and frailty in community-dwelling older adults using self-report data. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 59, M627–632.
Moayyeri, A., Hammond, C. J., Hart, D. J., & Spector, T. D. (2013a). The UK adult twin registry (TwinsUK Resource). Twin Research and Human Genetics, 16, 144149.
Moayyeri, A., Hammond, C. J., Valdes, M., & Spector, T. D. (2013b). Cohort profile: TwinsUK and healthy ageing twin study. International Journal of Epidemiology, 42, 7685.
Moreira, V. G., & Lourenco, R. A. (2013). Prevalence and factors associated with frailty in an older population from the city of Rio de Janeiro, Brazil: The FIBRA-RJ study. Clinics (Sao Paulo), 68, 979–785.
Neale, M. C., Walters, E. E., Eaves, L. J., Maes, H. H., & Kendler, K. S. (1994). Multivariate genetic analysis of twin-family data on fears: Mx models. Behavior Genetics, 24, 119139.
Needham, B. L., Smith, J. A., Zhao, W., Wang, X., Mukherjee, B., Kardia, S. L., . . . Diez Roux, A. V. (2015). Life course socioeconomic status and DNA methylation in genes related to stress reactivity and inflammation: The multi-ethnic study of atherosclerosis. Epigenetics, 10, 958969.
Office for National Statistics. (2005). The National Statistics Socio-Economic Classification. User Manual. London: Palgrave Macmillan.
Ortola, R., Garcia-Esquinas, E., Leon-Munoz, L. M., Guallar-Castillon, P., Valencia-Martin, J. L., Galan, I., & Rodriguez-Artalejo, F. (2016). Patterns of alcohol consumption and risk of frailty in community-dwelling older adults. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 71, 251258.
Peek, M. K., Howrey, B. T., Ternent, R. S., Ray, L. A., & Ottenbacher, K. J. (2012). Social support, stressors, and frailty among older Mexican American adults. The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences, 67, 755764.
Peeters, H., Van Gestel, S., Vlietinck, R., Derom, C., & Derom, R. (1998). Validation of a telephone zygosity questionnaire in twins of known zygosity. Behavior Genetics, 28, 159163.
Preacher, K. J., & Hayes, A. F. (2004). SPSS and SAS procedures for estimating indirect effects in simple mediation models. Behavior Research Methods, Instruments, and Computers, 36, 717731.
Purdie, D. M., Dunne, M. P., Boyle, F. M., Cook, M. D., & Najman, J. M. (2002). Health and demographic characteristics of respondents in an Australian national sexuality survey: Comparison with population norms. Journal of Epidemiology and Community Health, 56, 748753.
Richardson, K., & Norgate, S. (2005). The equal environments assumption of classical twin studies may not hold. British Journal of Educational Psychology, 75 (Pt 3), 339350.
Rockwood, K., Fox, R. A., Stolee, P., Robertson, D., & Beattie, B. L. (1994). Frailty in elderly people: An evolving concept. Canadian Medical Association Journal, 150, 489495.
Rockwood, R., Mitnitski, A., & Howlett, S. E. (2015). Frailty: Scaling from cellular deficit accumulation? Interdisciplinary Topics in Gerontology and Geriatrics, 41, 114.
Romero-Ortuno, R. (2014). Frailty index in Europeans: Association with determinants of health. Geriatrics and Gerontology International, 14, 420429.
Scarr, S. (1968). Environmental bias in twin studies. Eugenics Quarterly, 15, 3440.
Searle, S. D., Mitnitski, A., Gahbauer, E. A., Gill, T. M., & Rockwood, K. (2008). A standard procedure for creating a frailty index. BMC Geriatrics, 8, 24.
Spector, T. D., & Williams, F. M. (2006). The UK adult twin registry (TwinsUK). Twin Research and Human Genetics, 9, 899906.
Strawbridge, W. J., Shema, S. J., Balfour, J. L., Higby, H. R., & Kaplan, G. A.(1998). Antecedents of frailty over three decades in an older cohort. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 53, S9S16.
Szanton, S. L., Seplaki, C. L., Thorpe, R. J. Jr, Allen, J. K., & Fried, L. P. (2010). Socioeconomic status is associated with frailty: The women's health and aging studies. Journal of Epidemiology and Community Health, 64, 6367.
Theou, O., Brothers, T. D., Pena, F. G., Mitnitski, A., & Rockwood, K. (2014). Identifying common characteristics of frailty across seven scales. Journal of the American Geriatric Society, 62, 901906.
Tishler, P. V., & Carey, V. J. (2007). Can comparison of MZ- and DZ-twin concordance rates be used invariably to estimate heritability?. Twin Research and Human Genetics, 10, 712717.
Trevisan, C., Veronese, N., Maggi, S., Baggio, G., De Rui, M., Bolzetta, F., . . . Sergi, G. (2016). Marital status and frailty in older people: Gender differences in the Progetto Veneto Anziani longitudinal study. Journal of Women's Health, 25, 630637.
United Nations Children's Emergency Fund (UNICEF) and World Health Organization (WHO). (2004). Low birthweight: Country, regional and global estimates. New York: UNICEF.
Van Den Beld, A., Huhtaniemi, I. T., Pettersson, K. S., Pols, H. A., Grobbee, D. E., De Jong, F. H., & Lamberts, S. W. (1999). Luteinizing hormone and different genetic variants, as indicators of frailty in healthy elderly men. Journal of Clinical Endocrinology and Metabolism, 84, 13341339.
Walston, J., Arking, D. E., Fallin, D., Li, T., Beamer, B., Xue, Q., Ferrucci, L., . . . Chakravarti, A. (2005). IL-6 gene variation is not associated with increased serum levels of IL-6, muscle, weakness, or frailty in older women. Experimental Gerontology, 40, 344352.
Wang, C., Song, X., Mitnitski, A., Fang, X., Tang, Z., Yu, P., & Rockwood, K. (2014). Effect of health protective factors on health deficit accumulation and mortality risk in older adults in the Beijing longitudinal study of aging. Journal of the American Geriatric Society, 62, 821828.
Woo, J., Goggins, W., Sham, A., & Ho, S. C. (2005). Social determinants of frailty. Gerontology, 51, 402408.
Woods, N. F., LaCroix, A. Z., Gray, S. L., Aragaki, A., Cochrane, B. B., Brunner, R. L., Masaki, K., . . . Newman, A. B. (2005). Frailty: Emergence and consequences in women aged 65 and older in the women's health initiative observational study. Journal of the American Geriatric Society, 53: 13211330.
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