Browsing by Author "Harris, Tamara"

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    Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry
    (Wiley, 2019-07) Hsu, Yi-Hsiang; Estrada, Karol; Evangelou, Evangelos; Ackert-Bicknell, Cheryl; Akesson, Kristina; Beck, Thomas; Brown, Suzanne J.; Capellini, Terence; Carbone, Laura; Cauley, Jane; Cheung, Ching-Lung; Cummings, Steven R.; Czerwinski, Stefan; Demissie, Serkalem; Econs, Michael; Evans, Daniel; Farber, Charles; Gautvik, Kaare; Harris, Tamara; Kammerer, Candace; Kemp, John; Koller, Daniel L.; Kung, Annie; Lawlor, Debbie; Lee, Miryoung; Lorentzon, Mattias; McGuigan, Fiona; Medina-Gomez, Carolina; Mitchell, Braxton; Newman, Anne; Nielson, Carrie; Ohlsson, Claes; Peacock, Munro; Reppe, Sjur; Richards, J. Brent; Robbins, John; Sigurdsson, Gunnar; Spector, Timothy D.; Stefansson, Kari; Streeten, Elizabeth; Styrkarsdottir, Unnur; Tobias, Jonathan; Trajanoska, Katerina; Uitterlinden, André; Vandenput, Liesbeth; Wilson, Scott G.; Yerges-Armstrong, Laura; Young, Mariel; Zillikens, Carola; Rivadeneira, Fernando; Kiel, Douglas P.; Karasik, David; Medicine, School of Medicine
    Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with ∼2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p ≤ 2.6 × 10-8 ) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 × 10-5 ). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12% to 22% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility.
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    Prediction of sustained harmonic walking in the free-living environment using raw accelerometry data
    (IOP Publishing, 2018-02-28) Urbanek, Jacek K.; Zipunnikov, Vadim; Harris, Tamara; Fadel, William; Glynn, Nancy; Koster, Annemarie; Caserotti, Paolo; Crainiceanu, Ciprian; Harezlak, Jaroslaw; Biostatistics, School of Public Health
    OBJECTIVE: Using raw, sub-second-level accelerometry data, we propose and validate a method for identifying and characterizing walking in the free-living environment. We focus on sustained harmonic walking (SHW), which we define as walking for at least 10 s with low variability of step frequency. APPROACH: We utilize the harmonic nature of SHW and quantify the local periodicity of the tri-axial raw accelerometry data. We also estimate the fundamental frequency of the observed signals and link it to the instantaneous walking (step-to-step) frequency (IWF). Next, we report the total time spent in SHW, number and durations of SHW bouts, time of the day when SHW occurred, and IWF for 49 healthy, elderly individuals. MAIN RESULTS: The sensitivity of the proposed classification method was found to be 97%, while specificity ranged between 87% and 97% and the prediction accuracy ranged between 94% and 97%. We report the total time in SHW between 140 and 10 min d-1 distributed between 340 and 50 bouts. We estimate the average IWF to be 1.7 steps-per-second. SIGNIFICANCE: We propose a simple approach for the detection of SHW and estimation of IWF, based on Fourier decomposition.
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    Stride variability measures derived from wrist- and hip-worn accelerometers
    (Elsevier, 2017-02) Urbanek, Jacek K.; Harezlak, Jaroslaw; Glynn, Nancy W.; Harris, Tamara; Crainiceanu, Ciprian; Zipunnikov, Vadim; Biostatistics, School of Public Health
    Many epidemiological and clinical studies use accelerometry to objectively measure physical activity using the activity counts, vector magnitude, or number of steps. These measures use just a fraction of the information in the raw accelerometry data as they are typically summarized at the minute level. To address this problem, we define and estimate two measures of temporal stride-to-stride gait variability based on raw accelerometry data: Amplitude Deviation (AD) and Phase Deviation (PD). We explore the sensitivity of our approach to on-body placement of the accelerometer by comparing hip, left and right wrist placements. We illustrate the approach by estimating AD and PD in 46 elderly participants in the Developmental Epidemiologic Cohort Study (DECOS) who worn accelerometers during a 400m walk test. We also show that AD and PD have a statistically significant association with the gait speed and sit-to-stand test performance.