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Browsing by Author "Wactawski-Wende, Jean"
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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 Proton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative(Taylor & Francis, 2023) Ballinger, Tarah J.; Djuric, Zora; Sardesai, Sagar; Hovey, Kathleen M.; Andrews, Chris A.; Brasky, Theodore M.; Zhang, Jian Ting; Rohan, Thomas E.; Saquib, Nazmus; Shadyab, Aladdin H.; Simon, Michael; Wactawski-Wende, Jean; Wallace, Robert; Kato, Ikuko; Medicine, School of MedicineProton pump inhibitors (PPIs) have off-target activity on fatty acid synthase (FASN), a critical enzyme in energy balance and cancer growth. We evaluated risk of common obesity-related cancers: breast, colorectal (CRC), and endometrial, with use of PPI and histamine-2 receptor antagonists (H2RA) in 124,931 postmenopausal women enrolled in the Women's Health Initiative. Incident cancer cases were physician-adjudicated. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence after year 3. There were 7956 PPI ever users and 9398 H2RA only users. Ever use of either PPI or H2RA was not associated with risk of breast cancer (n = 9186) nor risk of endometrial cancer (n = 1231). The risk of CRC (n = 2280) was significantly lower in PPI users (HR = 0.75, 95% CI = 0.61-0.92), but not in H2RA users (HR = 1.13, 95% CI = 0.97-1.31). The association of PPI use with CRC was apparent regardless of BMI or NSAID use, and was stronger with longer PPI duration (p = 0.006) and potency (p = 0.005). The findings that PPI use, but not H2RA use, demonstrate an inverse dose-response relationship with risk of CRC is consistent with preclinical data showing FASN inhibition prevents colon cancer progression and supports a role of PPI in CRC prevention.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.