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
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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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    • "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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    • "The studies participating in the FNIH Sarcopenia Project are described in the first manuscript in this series (6). They include: Age, Gene and Environment Susceptibility-Reykjavik Study (AGES) (7); Boston Puerto Rican Health Study (BPRHS) (8); six clinical trials at University of Connecticut (UCONN) (9–14); Framingham Heart Study (FHS) Original cohort (15) and the Offspring cohort (16); Health, Aging, and Body Composition Study (HABC) (17); Invecchiare in Chianti (InChianti) (18); Osteoporotic Fractures in Men Study (MrOS) (19,20); Rancho Bernardo Study (RBS) (21); and Study of Osteoporotic Fractures (SOF) (22,23). To be included in these analyses, participants must be aged 65 and older and must have completed, at a single time point, the following measures: objectively measured body mass index (BMI), appendicular lean mass (ALM: sum of lean mass in the arms and legs), grip strength, and gait speed. "
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    ABSTRACT: Several consensus groups have previously published operational criteria for sarcopenia, incorporating lean mass with strength and/or physical performance. The purpose of this manuscript is to describe the prevalence, agreement, and discrepancies between the Foundation for the National Institutes of Health (FNIH) criteria with other operational definitions for sarcopenia. The FNIH Sarcopenia Project used data from nine studies including: Age, Gene and Environment Susceptibility-Reykjavik Study; Boston Puerto Rican Health Study; a series of six clinical trials from the University of Connecticut; Framingham Heart Study; Health, Aging, and Body Composition Study; Invecchiare in Chianti; Osteoporotic Fractures in Men Study; Rancho Bernardo Study; and Study of Osteoporotic Fractures. Participants included in these analyses were aged 65 and older and had measures of body mass index, appendicular lean mass, grip strength, and gait speed. The prevalence of sarcopenia and agreement proportions was higher in women than men. The lowest prevalence was observed with the FNIH criteria (1.3% men and 2.3% women) compared with the International Working Group and the European Working Group for Sarcopenia in Older Persons (5.1% and 5.3% in men and 11.8% and 13.3% in women, respectively). The positive percent agreements between the FNIH criteria and other criteria were low, ranging from 7% to 32% in men and 5% to 19% in women. However, the negative percent agreement were high (all >95%). The FNIH criteria result in a more conservative operational definition of sarcopenia, and the prevalence was lower compared with other proposed criteria. Agreement for diagnosing sarcopenia was low, but agreement for ruling out sarcopenia was very high. Consensus on the operational criteria for the diagnosis of sarcopenia is much needed to characterize populations for study and to identify adults for treatment.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 05/2014; 69(5):584-90. DOI:10.1093/gerona/glu013 · 5.42 Impact Factor
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