Harris, T. B. et al. Age, Gene/Environment Susceptibility-Reykjavik Study: multidisciplinary applied phenomics. Am. J. Epidemiol. 165, 1076-1087

Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD 20892-9205, USA.
American Journal of Epidemiology (Impact Factor: 5.23). 06/2007; 165(9):1076-87. DOI: 10.1093/aje/kwk115
Source: PubMed


In anticipation of the sequencing of the human genome and description of the human proteome, the Age, Gene/Environment Susceptibility–Reykjavik
Study (AGES–Reykjavik) was initiated in 2002. AGES–Reykjavik was designed to examine risk factors, including genetic susceptibility
and gene/environment interaction, in relation to disease and disability in old age. The study is multidisciplinary, providing
detailed phenotypes related to the cardiovascular, neurocognitive (including sensory), and musculoskeletal systems, and to
body composition and metabolic regulation. Relevant quantitative traits, subclinical indicators of disease, and medical diagnoses
are identified by using biomarkers, imaging, and other physiologic indicators. The AGES–Reykjavik sample is drawn from an
established population-based cohort, the Reykjavik Study. This cohort of men and women born between 1907 and 1935 has been
followed in Iceland since 1967 by the Icelandic Heart Association. The AGES–Reykjavik cohort, with cardiovascular risk factor
assessments earlier in life and detailed late-life phenotypes of quantitative traits, will create a comprehensive study of
aging nested in a relatively genetically homogeneous older population. This approach should facilitate identification of genetic
factors that contribute to healthy aging as well as the chronic conditions common in old age.

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    • "Study participants underwent a comprehensive evaluation that included questions on medical history, lifestyle, and family history and had a series of standardized health examinations and laboratory testing, including analyses of morning and evening salivary samples. In addition, data from hospitalization records and cause of death registries were linked to the participant data (Harris et al., 2007). "
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    ABSTRACT: Lower educational attainment generally is a strong predictor of coronary heart disease (CHD). The underlying mechanisms of this effect are, however, less clear. One hypothesis is that stress related to limitations imposed by lower socioeconomic status elicits changes in hypothalamic-pituitary-adrenal axis functioning, which, in turn, increases risk of CHD. In a large cohort study, we examined whether educational attainment was related to risk of fatal and non-fatal CHD and the extent to which salivary cortisol mediated this relation independent of potential confounders, including lifestyles. Data came from 3723 participants aged 66 through 96 from the Age, Gene/Environment Susceptibility (AGES) - Reykjavik Study. Between 2002 and 2006, data were collected using questionnaires and examinations including morning and evening salivary samples. Hospital admission records and cause of death registries (ICD-9 and ICD-10 codes) were available until December 2009. Linear regression and Cox proportional hazards analyses were performed. Even after adjustment for potential confounders, including lifestyle, persons with lower educational attainment showed a blunted cortisol response and also greater risk of incident CHD. However, our data did not support the role of cortisol as a mediator in the association between education and CHD in an older sample (192).
    Social Science & Medicine 09/2014; 127. DOI:10.1016/j.socscimed.2014.09.050 · 2.89 Impact Factor
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    • "In 2002–2006, adults aged ≥65 years who originally participated in the Reykjavik Study (1967–1997) were recruited to participate in an interdisciplinary genetic epidemiology study of the musculoskeletal, body composition, neurocognitive, and vascular systems including assessment of function by both self-report and performance (16). The objective of the study was to identify shared biological pathways for disease and to test gene–environment interactions. "
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    ABSTRACT: Low muscle mass and weakness are common and potentially disabling in older adults, but in order to become recognized as a clinical condition, criteria for diagnosis should be based on clinically relevant thresholds and independently validated. The Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project used an evidence-based approach to develop these criteria. Initial findings were presented at a conference in May 2012, which generated recommendations that guided additional analyses to determine final recommended criteria. Details of the Project and its findings are presented in four accompanying manuscripts. The Foundation for the National Institutes of Health Sarcopenia Project used data from nine sources of community-dwelling older persons: Age, Gene/Environment Susceptibility-Reykjavik Study, Boston Puerto Rican Health Study, a series of six clinical trials, Framingham Heart Study, Health, Aging, and Body Composition, Invecchiare in Chianti, Osteoporotic Fractures in Men Study, Rancho Bernardo Study, and Study of Osteoporotic Fractures. Feedback from conference attendees was obtained via surveys and breakout groups. The pooled sample included 26,625 participants (57% women, mean age in men 75.2 [±6.1 SD] and in women 78.6 [±5.9] years). Conference attendees emphasized the importance of evaluating the influence of body mass on cutpoints. Based on the analyses presented in this series, the final recommended cutpoints for weakness are grip strength <26kg for men and <16kg for women, and for low lean mass, appendicular lean mass adjusted for body mass index <0.789 for men and <0.512 for women. These evidence-based cutpoints, based on a large and diverse population, may help identify participants for clinical trials and should be evaluated among populations with high rates of functional limitations.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 05/2014; 69(5):547-58. DOI:10.1093/gerona/glu010 · 5.42 Impact Factor
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    • "Data available for this phase of the FNIH Sarcopenia Project analysis included: the Study of Osteoporotic Fractures, both the original cohort (study Visit 6) (14) and African American cohort (study Visit 1) (15); the Osteoporotic Fractures in Men Study (baseline visit) (16); the Health, Aging and Body Composition Study (Year 6 Clinic Visit) (17); the Framingham Study (both the Offspring cohort [exam cycles 6 and 7, 1996–2001] (18) and Original cohort [exam cycle 26, 1999–2001]) (19); the InCHIANTI Study (Aging in the Chianti Area, Year 3 visit) (20); the Boston Puerto Rican Health Study (baseline visit) (21); the Age, Gene/Environment Susceptibility-Reykjavik Study (baseline visit) (22); and four clinical trials from the University of Connecticut (UCONN, randomization visit for all studies) (23–26). "
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    ABSTRACT: Weakness is common and contributes to disability, but no consensus exists regarding a strength cutpoint to identify persons at high risk. This analysis, conducted as part of the Foundation for the National Institutes of Health Sarcopenia Project, sought to identify cutpoints that distinguish weakness associated with mobility impairment, defined as gait speed less than 0.8 m/s. In pooled cross-sectional data (9,897 men and 10,950 women), Classification and Regression Tree analysis was used to derive cutpoints for grip strength associated with mobility impairment. In men, a grip strength of 26-32 kg was classified as "intermediate" and less than 26 kg as "weak"; 11% of men were intermediate and 5% were weak. Compared with men with normal strength, odds ratios for mobility impairment were 3.63 (95% CI: 3.01-4.38) and 7.62 (95% CI 6.13-9.49), respectively. In women, a grip strength of 16-20 kg was classified as "intermediate" and less than 16 kg as "weak"; 25% of women were intermediate and 18% were weak. Compared with women with normal strength, odds ratios for mobility impairment were 2.44 (95% CI 2.20-2.71) and 4.42 (95% CI 3.94-4.97), respectively. Weakness based on these cutpoints was associated with mobility impairment across subgroups based on age, body mass index, height, and disease status. Notably, in women, grip strength divided by body mass index provided better fit relative to grip strength alone, but fit was not sufficiently improved to merit different measures by gender and use of a more complex measure. Cutpoints for weakness derived from this large, diverse sample of older adults may be useful to identify populations who may benefit from interventions to improve muscle strength and function.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 05/2014; 69(5):559-66. DOI:10.1093/gerona/glu011 · 5.42 Impact Factor
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