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Browsing by Author "Cauley, Jane A."
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Item Disentangling the genetics of lean mass(Oxford University Press, 2019-02-01) Karasik, David; Zillikens, M. Carola; Hsu, Yi-Hsiang; Aghdassi, Ali; Akesson, Kristina; Amin, Najaf; Barroso, Inês; Bennett, David A.; Bertram, Lars; Bochud, Murielle; Borecki, Ingrid B.; Broer, Linda; Buchman, Aron S.; Byberg, Liisa; Campbell, Harry; Campos-Obando, Natalia; Cauley, Jane A.; Cawthon, Peggy M.; Chambers, John C.; Chen, Zhao; Cho, Nam H.; Choi, Hyung Jin; Chou, Wen-Chi; Cummings, Steven R.; De Groot, Lisette C. P. G. M.; De Jager, Phillip L.; Demuth, Ilja; Diatchenko, Luda; Econs, Michael J.; Eiriksdottir, Gudny; Enneman, Anke W.; Eriksson, Joel; Eriksson, Johan G.; Estrada, Karol; Evans, Daniel S.; Feitosa, Mary F.; Fu, Mao; Gieger, Christian; Grallert, Harald; Gudnason, Vilmundur; Lenore, Launer J.; Hayward, Caroline; Hofman, Albert; Homuth, Georg; Huffman, Kim M.; Husted, Lise B.; Illig, Thomas; Ingelsson, Erik; Ittermann, Till; Jansson, John-Olov; Johnson, Toby; Biffar, Reiner; Jordan, Joanne M.; Jula, Antti; Karlsson, Magnus; Khaw, Kay-Tee; Kilpeläinen, Tuomas O.; Klopp, Norman; Kloth, Jacqueline S. L.; Koller, Daniel L.; Kooner, Jaspal S.; Kraus, William E.; Kritchevsky, Stephen; Kutalik, Zoltán; Kuulasmaa, Teemu; Kuusisto, Johanna; Laakso, Markku; Lahti, Jari; Lang, Thomas; Langdahl, Bente L.; Lerch, Markus M.; Lewis, Joshua R.; Lill, Christina; Lind, Lars; Lindgren, Cecilia; Liu, Yongmei; Livshits, Gregory; Ljunggren, Östen; Loos, Ruth J. F.; Lorentzon, Mattias; Luan, Jian'an; Luben, Robert N.; Malkin, Ida; McGuigan, Fiona E.; Medina-Gomez, Carolina; Meitinger, Thomas; Melhus, Håkan; Mellström, Dan; Michaëlsson, Karl; Mitchell, Braxton D.; Morris, Andrew P.; Mosekilde, Leif; Nethander, Maria; Newman, Anne B.; O'Connell, Jeffery R.; Oostra, Ben A.; Orwoll, Eric S.; Palotie, Aarno; Peacock, Munro; Perola, Markus; Peters, Annette; Prince, Richard L.; Psaty, Bruce M.; Räikkönen, Katri; Ralston, Stuart H.; Ripatti, Samuli; Rivadeneira, Fernando; Robbins, John A.; Rotter, Jerome I.; Rudan, Igor; Salomaa, Veikko; Satterfield, Suzanne; Schipf, Sabine; Shin, Chan Soo; Smith, Albert V.; Smith, Shad B.; Soranzo, Nicole; Spector, Timothy D.; Stančáková, Alena; Stefansson, Kari; Steinhagen-Thiessen, Elisabeth; Stolk, Lisette; Streeten, Elizabeth A.; Styrkarsdottir, Unnur; Swart, Karin M. A.; Thompson, Patricia; Thomson, Cynthia A.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tikkanen, Emmi; Tranah, Gregory J.; Uitterlinden, André G.; Van Duijn, Cornelia M.; Van Schoor, Natasja M.; Vandenput, Liesbeth; Vollenweider, Peter; Völzke, Henry; Wactawski-Wende, Jean; Walker, Mark; Wareham, Nicholas J.; Waterworth, Dawn; Weedon, Michael N.; Wichmann, H-Erich.; Widen, Elisabeth; Williams, Frances M. K.; Wilson, James F.; Wright, Nicole C.; Yerges-Armstrong, Laura M.; Yu, Lei; Zhang, Weihua; Zhao, Jing Hua; Zhou, Yanhua; Nielson, Carrie M.; Harris, Tamara B.; Demissie, Serkalem; Kiel, Douglas P.; Ohlsson, Claes; Medicine, School of MedicineBackground: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.Item Racial/Ethnic Differences in 25-Hydroxy Vitamin D and Parathyroid Hormone Levels and Cardiovascular Disease Risk Among Postmenopausal Women(American Heart Association, 2019-02-19) Zhang, Xi; Tu, Wanzhu; Manson, JoAnn E.; Tinker, Lesley; Liu, Simin; Cauley, Jane A.; Qi, Lihong; Mouton, Charles; Martin, Lisa W.; Hou, Lifang; Song, Yiqing; Epidemiology, School of Public HealthBackground Recent evidence suggests that racial/ethnic differences in circulating levels of free or bioavailable 25-hydroxy vitamin D (25[ OH ]D) rather than total 25( OH )D may explain apparent racial disparities in cardiovascular disease ( CVD ). We prospectively examined black-white differences in the associations of total, free, and bioavailable 25( OH )D, vitamin D-binding protein, and parathyroid hormone levels at baseline with incident CVD (including nonfatal myocardial infarction, nonfatal stroke, and CVD death) in postmenopausal women. Methods and Results We conducted a case-cohort study among 79 705 postmenopausal women, aged 50 to 79 years, who were free of CVD at baseline in the WHI-OS (Women's Health Initiative Observational Study). A subcohort of 1300 black and 1500 white participants were randomly chosen as controls; a total of 550 black and 1500 white women who developed incident CVD during a mean follow-up of 11 years were chosen as cases. We directly measured total 25( OH )D, vitamin D-binding protein, albumin, parathyroid hormone, and calculated free and bioavailable 25( OH )D. Weighted Cox proportional hazards models were used to examine their associations with CVD risk. Although vitamin D-binding protein and total, free, and bioavailable 25( OH )D were not significantly associated with CVD risk in black or white women, a significant positive association between parathyroid hormone and CVD risk persisted in white women (hazard ratio comparing the highest quartile with the lowest, 1.37; 95% CI , 1.06-1.77) but not in black women (hazard ratio comparing the highest quartile with the lowest, 1.12; 95% CI, 0.79-1.58), independent of total, free, and bioavailable 25( OH )D or vitamin D-binding protein. Conclusions Circulating levels of vitamin D biomarkers are not related to CVD risk in either white or black women. Higher parathyroid hormone levels may be an independent risk factor for CVD in white women.Item Vitamin D levels and menopause-related symptoms.(Wolters Kluwer Health, 2014-11) LeBlanc, Erin S.; Desai, Manisha; Perrin, Nancy; Wactawski-Wende, Jean; Manson, JoAnn E.; Cauley, Jane A.; Michael, Yvonne L.; Tang, Jean; Womack, Catherine; Song, Yiqing; Johnson, Karen C.; O’Sullivan, Mary J.; Woods, Nancy; Stefanick, Marcia L.; Department of Epidemiology, Richard M. Fairbanks School of Public HealthObjective: To determine whether vitamin D levels are associated with menopause-related symptoms in older women. Methods: A randomly selected subset of 1,407 women, among 26,104 potentially eligible participants of the Women’s Health Initiative Calcium and Vitamin D (CaD) trial of postmenopausal women aged 51-80 years, had 25-hydroxyvitamin D [25(OH)D] levels measured at the CaD trial baseline visit. Information about menopause-related symptoms at baseline was obtained by questionnaire and included overall number of symptoms and composite measures of sleep disturbance, emotional well-being, and energy/fatigue, as well as individual symptoms. After exclusions for missing data, 530 women [mean age 66.2 years (SD 6.8)] were included in these analyses. Results: There were borderline significant associations between 25(OH)D levels and total number of menopausal symptoms (p values ranging from 0.05 to 0.06 for fully adjusted models); however, the effect was clinically insignificant and disappeared with correction for multiple testing. There were no associations between 25(OH)D levels and composite measures of sleep disturbance, emotional well-being, or energy/fatigue (p’s > 0.10 for fully adjusted models). Conclusions: There was no evidence of a clinically important association between serum 25(OH)D levels and menopause-related symptoms in postmenopausal women.