Browsing by Author "Newman, Anne B"

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Open Access
A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.
(J Gerontol A Biol Sci Med Sci, 2010-05) Newman, Anne B; Walter, Stefan; Lunetta, Kathryn L; Garcia, Melissa E; Slagboom, P Eline; Christensen, Kaare; Arnold, Alice M; Aspelund, Thor; Aulchenko, Yurii S; Benjamin, Emelia J; Christiansen, Lene; D'Agostino, Ralph B; Fitzpatrick, Annette L; Franceschini, Nora; Glazer, Nicole L; Gudnason, Vilmundur; Hofman, Albert; Kaplan, Robert; Karasik, David; Kelly-Hayes, Margaret; Kiel, Douglas P; Launer, Lenore J; Marciante, Kristin D; Massaro, Joseph M; Miljkovic, Iva; Nalls, Michael A; Hernandez, Dena; Psaty, Bruce M; Rivadeneira, Fernando; Rotter, Jerome; Seshadri, Sudha; Smith, Albert V; Taylor, Kent D; Tiemeier, Henning; Uh, Hae-Won; Uitterlinden, André G; Vaupel, James W; Walston, Jeremy; Westendorp, Rudi GJ; Harris, Tamara B; Lumley, Thomas; van Duijn, Cornelia M; Murabito, Joanne M
BACKGROUND: Genome-wide association studies (GWAS) may yield insights into longevity. METHODS: We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort. RESULTS: There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x 10(-8). Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x 10(-7) for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage. CONCLUSION: Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings.
Open Access
A Modified Healthy Aging Index and Its Association with Mortality: The National Health and Nutrition Examination Survey, 1999–2002
(The Journals of Gerontology: Series A, 2017-10) Wu, Chenkai; Smit, Ellen; Sanders, Jason L; Newman, Anne B; Odden, Michelle C
Open Access
Blood Pressure Trajectory, Gait Speed, and Outcomes: The Health, Aging, and Body Composition Study
(The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2016-12) Odden, Michelle C; Wu, Chenkai; Shlipak, Michael G; Psaty, Bruce M; Katz, Ronit; Applegate, William B; Harris, Tamara; Newman, Anne B; Peralta, Carmen A; Health ABC Study
Open Access
Do gender, disability, and morbidity affect aging rate in the LLFS? Application of indices of cumulative deficits.
(Mech Ageing Dev, 2011-04) Kulminski, Alexander M; Arbeev, Konstantin G; Christensen, Kaare; Mayeux, Richard; Newman, Anne B; Province, Michael A; Hadley, Evan C; Rossi, Winifred; Perls, Thomas T; Elo, Irma T; Yashin, Anatoli I
We used an approach of cumulative deficits to evaluate the rate of aging in 4954 participants of the Long-Life Family Study (LLFS) recruited in the U.S. (Boston, New York, and Pittsburgh) and Denmark. We used an array of 85 health-related deficits covering major health dimensions including depression, cognition, morbidity, physical performance, and disability to construct several deficit indices (DIs) with overlapping and complementary sets of deficits to test robustness of the estimates. Our study shows that the DIs robustly characterize accelerated rates of aging irrespective of specific of deficits. When a wider spectrum of health dimensions is considered these rates are better approximated by quadratic law. Exponential rates are more characteristic for more severe health dimensions. The aging rates are the same for males and females. Individuals who contracted major diseases and those who were free of them exhibited the same aging rates as characterized by the DI constructed using mild deficits. Unlike health, disability can qualitatively alter the aging patterns of the LLFS participants. We report on systemic differences in health among the LLFS centenarians residing in New York and Boston. This study highlights importance of aggregated approaches to better understand systemic mechanisms of health deterioration in long-living individuals.
Open Access
Health and function of participants in the Long Life Family Study: A comparison with other cohorts.
(Aging (Albany NY), 2011-01) Newman, Anne B; Glynn, Nancy W; Taylor, Christopher A; Sebastiani, Paola; Perls, Thomas T; Mayeux, Richard; Christensen, Kaare; Zmuda, Joseph M; Barral, Sandra; Lee, Joseph H; Simonsick, Eleanor M; Walston, Jeremy D; Yashin, Anatoli I; Hadley, Evan
Individuals from families recruited for the Long Life Family Study (LLFS) (n= 4559) were examined and compared to individuals from other cohorts to determine whether the recruitment targeting longevity resulted in a cohort of individuals with better health and function. Other cohorts with similar data included the Cardiovascular Health Study, the Framingham Heart Study, and the New England Centenarian Study. Diabetes, chronic pulmonary disease and peripheral artery disease tended to be less common in LLFS probands and offspring compared to similar aged persons in the other cohorts. Pulse pressure and triglycerides were lower, high density lipids were higher, and a perceptual speed task and gait speed were better in LLFS. Age-specific comparisons showed differences that would be consistent with a higher peak, later onset of decline or slower rate of change across age in LLFS participants. These findings suggest several priority phenotypes for inclusion in future genetic analysis to identify loci contributing to exceptional survival.
Open Access
Heritability estimates of endophenotypes of long and health life: the Long Life Family Study.
(J Gerontol A Biol Sci Med Sci, 2010-12) Matteini, Amy M; Fallin, M Daniele; Kammerer, Candace M; Schupf, Nicole; Yashin, Anatoli I; Christensen, Kaare; Arbeev, Konstantin G; Barr, Graham; Mayeux, Richard; Newman, Anne B; Walston, Jeremy D
BACKGROUND: Identification of gene variants that contribute to exceptional survival may provide critical biologic information that informs optimal health across the life span. METHODS: As part of phenotype development efforts for the Long Life Family Study, endophenotypes that represent exceptional survival were identified and heritability estimates were calculated. Principal components (PCs) analysis was carried out using 28 physiologic measurements from five trait domains (cardiovascular, cognition, physical function, pulmonary, and metabolic). RESULTS: The five most dominant PCs accounted for 50% of underlying trait variance. The first PC (PC1), which consisted primarily of poor pulmonary and physical function, represented 14.3% of the total variance and had an estimated heritability of 39%. PC2 consisted of measures of good metabolic and cardiovascular function with an estimated heritability of 27%. PC3 was made up of cognitive measures (h(2) = 36%). PC4 and PC5 contained measures of blood pressure and cholesterol, respectively (h(2) = 25% and 16%). CONCLUSIONS: These PCs analysis-derived endophenotypes may be used in genetic association studies to help identify underlying genetic mechanisms that drive exceptional survival in this and other populations.
Open Access
Visit-to-Visit Blood Pressure Variability and Mortality and Cardiovascular Outcomes Among Older Adults: The Health, Aging, and Body Composition Study
(American Journal of Hypertension, 2017-02) Wu, Chenkai; Shlipak, Michael G; Stawski, Robert S; Peralta, Carmen A; Psaty, Bruce M; Harris, Tamara B; Satterfield, Suzanne; Shiroma, Eric J; Newman, Anne B; Odden, Michelle C; Health ABC Study