Browsing by Author "Koster, Annemarie"

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    A Genome-Wide Association Meta-Analysis of Circulating Sex Hormone–Binding Globulin Reveals Multiple Loci Implicated in Sex Steroid Hormone Regulation
    (Public Library of Science, 2012) Coviello, Andrea D.; Haring, Robin; Wellons, Melissa; Vaidya, Dhananjay; Lehtimäki, Terho; Keildson, Sarah; Lunetta, Kathryn L.; He, Chunyan; Fornage, Myriam; Lagou, Vasiliki; Mangino, Massimo; Onland-Moret, N. Charlotte; Chen, Brian; Eriksson, Joel; Garcia, Melissa; Liu, Yong Mei; Koster, Annemarie; Lohman, Kurt; Lyytikäinen, Leo-Pekka; Petersen, Ann-Kristin; Prescott, Jennifer; Stolk, Lisette; Vandenput, Liesbeth; Wood, Andrew R.; Zhuang, Wei Vivian; Ruokonen, Aimo; Hartikainen, Anna-Liisa; Pouta, Anneli; Bandinelli, Stefania; Biffar, Reiner; Brabant, Georg; Cox, David G.; Chen, Yuhui; Cummings, Steven; Ferrucci, Luigi; Gunter, Marc J.; Hankinson, Susan E.; Martikainen, Hannu; Hofman, Albert; Homuth, Georg; Illig, Thomas; Jansson, John-Olov; Johnson, Andrew D.; Karasik, David; Karlsson, Magnus; Kettunen, Johannes; Kiel, Douglas P.; Kraft, Peter; Liu, Jingmin; Ljunggren, Östen; Lorentzon, Mattias; Maggio, Marcello; Markus, Marcello R. P.; Mellström, Dan; Miljkovic, Iva; Mirel, Daniel; Nelson, Sarah; Papunen, Laure Morin; Peeters, Petra H. M.; Prokopenko, Inga; Raffel, Leslie; Reincke, Martin; Reiner, Alex P.; Rexrode, Kathryn; Rivadeneira, Fernando; Schwartz, Stephen M.; Siscovick, David; Soranzo, Nicole; Stöckl, Doris; Tworoger, Shelley; Uitterlinden, André G.; van Gils, Carla H.; Vasan, Ramachandran S.; Wichmann, H-Erich; Zhai, Guangju; Bhasin, Shalender; Bidlingmaier, Martin; Chanock, Stephen J.; De Vivo, Immaculata; Harris, Tamara B.; Hunter, David J.; Kähönen, Mika; Liu, Simin; Ouyang, Pamela; Spector, Tim D.; van der Schouw, Yvonne T.; Viikari, Jorma; Wallaschofski, Henri; McCarthy, Mark I.; Frayling, Timothy M.; Murray, Anna; Franks, Steve; Järvelin, Marjo-Riitta; de Jong, Frank H.; Raitakari, Olli; Teumer, Alexander; Ohlsson, Claes; Murabito, Joanne M.; Perry, John R. B.; Medicine, School of Medicine
    Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8 × 10(-106)), PRMT6 (rs17496332, 1p13.3, p = 1.4 × 10(-11)), GCKR (rs780093, 2p23.3, p = 2.2 × 10(-16)), ZBTB10 (rs440837, 8q21.13, p = 3.4 × 10(-09)), JMJD1C (rs7910927, 10q21.3, p = 6.1 × 10(-35)), SLCO1B1 (rs4149056, 12p12.1, p = 1.9 × 10(-08)), NR2F2 (rs8023580, 15q26.2, p = 8.3 × 10(-12)), ZNF652 (rs2411984, 17q21.32, p = 3.5 × 10(-14)), TDGF3 (rs1573036, Xq22.3, p = 4.1 × 10(-14)), LHCGR (rs10454142, 2p16.3, p = 1.3 × 10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7 × 10(-08)), and UGT2B15 (rs293428, 4q13.2, p = 5.5 × 10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5 × 10(-08), women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ~15.6% and ~8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
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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.