Bone strength, or the ability to resist fractures, is critically dependent on bone health in young and middle years - the higher the peak bone mass achieved in younger years, the lower the likelihood of developing osteoporosis in later life. We postulate that social and psychological factors over the lifespan affect bone strength by influencing the level of peak strength achieved in young adulthood, the maintenance of bone strength through middle adulthood, and the rate of decline in older ages.
Our specific aims are to:
Aim 1. Determine the strength of the association between long-term psychosocial profiles and bone strength.
Aim 2. Determine the strength of the association between biological system dysregulation and bone strength.
Aim 3. Determine the extent to which the putative biological pathways mediate the associations between long- term psychosocial profiles and bone strength. The project will draw on three cohort studies (Midlife in the United States, the Wisconsin Study of Late Life Resilience, and the MacArthur Study of Successful Aging) that together, have data from adults, ages 24 and up, and have 9 or more years of follow up. This project is uniquely optimized to explore this thesis because: 1) In addition to using standard bone mineral density assessments, we will expand bone health outcomes to include comprehensive assessments of bone strength and bone metabolic balance. 2) We will determine the influence not only of social adversity and psychological ill-health but also of social advantage and psychological well-being on bone outcomes. 3) A lifespan perspective will be adopted, wherein long-term psychosocial influences will be used as predictors of adult bone strength. This project will be the first comprehensive attempt to delineate the influences of multiple psychosocial domains over the life course (including early life experiences) on bone strength, and to identify the biological pathways through which these influences are exerted. Its strengths lie in the unmatched breadth, depth, and longitudinal aspect of psychosocial and biological assessments in the 3 cohort studies, the complementary breadth and depth of bone outcomes assessed across the 3 studies, the lengths of follow up, the large range of ages spanned, and the novel approach to the research questions: the adoption of the more appropriate life- history approach to estimating psychosocial influences on bone strength, the equal consideration given to psychosocial advantage and adversity, and the innovative and comprehensive assessment of bone strength, that goes beyond the usual bone density metric of strength.

Public Health Relevance

This project will determine how bone strength (i.e., bone's ability to resist fracture) is affected by life histories of socioeconomic status (financial condition and social status), social relationships (with parents, spouse, friends, children, etc.), and psychological health (both positive aspects such as happiness, life satisfaction, personal growth and purpose in life, and negative ones, such as depression and anxiety). We will also examine which biological changes might explain these social and psychological effects on bone health. Discovery of these effects on bone strength and the biological mechanisms will mean that we can identify and target those at high risk for fractures for early screening and interventions, with the eventual goal of reducing the burden of osteoporosis (low bone strength) on quality of life and mortality.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG033067-03
Application #
8118476
Study Section
Social Sciences and Population Studies Study Section (SSPS)
Program Officer
Nielsen, Lisbeth
Project Start
2009-09-15
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
3
Fiscal Year
2011
Total Cost
$345,560
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Majumdar, Arunabha; Haldar, Tanushree; Bhattacharya, Sourabh et al. (2018) An efficient Bayesian meta-analysis approach for studying cross-phenotype genetic associations. PLoS Genet 14:e1007139
de Smith, Adam J; Walsh, Kyle M; Francis, Stephen S et al. (2018) BMI1 enhancer polymorphism underlies chromosome 10p12.31 association with childhood acute lymphoblastic leukemia. Int J Cancer 143:2647-2658
Ni, Guiyan; Moser, Gerhard; Schizophrenia Working Group of the Psychiatric Genomics Consortium et al. (2018) Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum Likelihood. Am J Hum Genet 102:1185-1194
Small, Kerrin S; Todor?evi?, Marijana; Civelek, Mete et al. (2018) Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition. Nat Genet 50:572-580
Wiemels, Joseph L; Walsh, Kyle M; de Smith, Adam J et al. (2018) GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21. Nat Commun 9:286
Scott, Robert A; Scott, Laura J; Mägi, Reedik et al. (2017) An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans. Diabetes 66:2888-2902
Lee, S Hong; Weerasinghe, W M Shalanee P; Wray, Naomi R et al. (2017) Using information of relatives in genomic prediction to apply effective stratified medicine. Sci Rep 7:42091
Cook, James P; Morris, Andrew P (2016) Multi-ethnic genome-wide association study identifies novel locus for type 2 diabetes susceptibility. Eur J Hum Genet 24:1175-80
Murk, William; DeWan, Andrew T (2016) Exhaustive Genome-Wide Search for SNP-SNP Interactions Across 10 Human Diseases. G3 (Bethesda) 6:2043-50
Shieh, Albert; Ishii, Shinya; Greendale, Gail A et al. (2016) Urinary N-telopeptide and Rate of Bone Loss Over the Menopause Transition and Early Postmenopause. J Bone Miner Res 31:2057-2064

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