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Browsing by Author "Shadyab, Aladdin H."
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Item Combined associations of 25-hydroxivitamin D and parathyroid hormone with diabetes risk and associated comorbidities among U.S. white and black women(Springer Nature, 2021-09) Xia, Jin; Tu, Wanzhu; Manson, JoAnn E.; Nan, Hongmei; Shadyab, Aladdin H.; Bea, Jennifer W.; Gower, Emily W.; Qi, Lihong; Cheng, Ting-Yuan David; Song, Yiqing; Epidemiology, School of Public HealthBackground/objectives: There is evidence of black-white differences in vitamin D status and cardiometabolic health. This study aimed to further evaluate the joint associations of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) with risks of diabetes and related cardiometabolic comorbidities among white and black women. Subjects/methods: We cross-sectionally and prospectively analyzed data from 1850 black and 3000 white postmenopausal women without cardiovascular disease or dialysis at baseline from the Women's Health Initiative-Observational Study. Weighted Cox proportional hazards analyses and weighted logistic regression models were used to examine the joint associations of 25(OH)D and PTH with incident diabetes and prevalence of other diabetes-related cardiometabolic comorbidities (including CKD, hypertension, or obesity). Results: We identified 3322 cases of obesity (n = 1629), hypertension (n = 2759), or CKD (n = 318) at baseline and 453 incident cases of diabetes during 11 years of follow-up. Cross-sectionally, lower 25(OH)D and higher PTH were independently associated with higher prevalence of hypertension [odds ratio (OR) = 0.79; 95% confidence interval (CI): 0.72-0.87 and OR = 1.55; 95% CI: 1.39-1.73] among white women only. When stratified by diabetes status, compared to women with 25(OH)D ≥50 nmol/L and PTH ≤6.89 pmol/L (65 pg/mL), women who did not have diabetes with vitamin D deficiency (<50 nmol/L) and PTH excess (>6.89 pmol/L) had higher prevalence of CKD, hypertension, or obesity (OR = 4.23; 95% CI: 2.90-6.18) than women who had diabetes (OR = 1.89; 95% CI: 0.96-3.71). Prospectively, lower 25(OH)D was associated with lower diabetes incidence [hazard ratio (HR) = 0.73; 95% CI: 0.62-0.86] in white women. Jointly, compared to the group with 25(OH)D ≥50 nmol/L and PTH ≤6.89 pmol/L, white women with 25(OH)D deficiency (<50 nmol/L) had elevated risk for diabetes, regardless of PTH levels. Conclusions: Low 25(OH)D and high PTH were jointly associated with increased risk of diabetes among white women only. Their joint associations with high prevalence of CKD, hypertension, and obesity were more pronounced among women without diabetes.Item Investigating Gene-Diet Interactions Impacting the Association Between Macronutrient Intake and Glycemic Traits(American Diabetes Association, 2023) Westerman, Kenneth E.; Walker, Maura E.; Gaynor, Sheila M.; Wessel, Jennifer; DiCorpo, Daniel; Ma, Jiantao; Alonso, Alvaro; Aslibekyan, Stella; Baldridge, Abigail S.; Bertoni, Alain G.; Biggs, Mary L.; Brody, Jennifer A.; Chen, Yii-Der Ida; Dupuis, Joseé; Goodarzi, Mark O.; Guo, Xiuqing; Hasbani, Natalie R.; Heath, Adam; Hidalgo, Bertha; Irvin, Marguerite R.; Johnson, W. Craig; Kalyani, Rita R.; Lange, Leslie; Lemaitre, Rozenn N.; Liu, Ching-Ti; Liu, Simin; Moon, Jee-Young; Nassir, Rami; Pankow, James S.; Pettinger, Mary; Raffield, Laura M.; Rasmussen-Torvik, Laura J.; Selvin, Elizabeth; Senn, Mackenzie K.; Shadyab, Aladdin H.; Smith, Albert V.; Smith, Nicholas L.; Steffen, Lyn; Talegakwar, Sameera; Taylor, Kent D.; de Vries, Paul S.; Wilson, James G.; Wood, Alexis C.; Yanek, Lisa R.; Yao, Jie; Zheng, Yinan; Boerwinkle, Eric; Morrison, Alanna C.; Fornage, Miriam; Russell, Tracy P.; Psaty, Bruce M.; Levy, Daniel; Heard-Costa, Nancy L.; Ramachandran, Vasan S.; Mathias, Rasika A.; Arnett, Donna K.; Kaplan, Robert; North, Kari E.; Correa, Adolfo; Carson, April; Rotter, Jerome I.; Rich, Stephen S.; Manson, JoAnn E.; Reiner, Alexander P.; Kooperberg, Charles; Florez, Jose C.; Meigs, James B.; Merino, Jordi; Tobias, Deirdre K.; Chen, Han; Manning, Alisa K.; Epidemiology, Richard M. Fairbanks School of Public HealthFew studies have demonstrated reproducible gene-diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient-glycemia relationship in genetically and culturally diverse cohorts. We analyzed 33,187 participants free of diabetes from 10 National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program cohorts with whole-genome sequencing, self-reported diet, and glycemic trait data. We fit cohort-specific, multivariable-adjusted linear mixed models for the effect of diet, modeled as an isocaloric substitution of carbohydrate for fat, and its interactions with common and rare variants genome-wide. In main effect meta-analyses, participants consuming more carbohydrate had modestly lower glycemic trait values (e.g., for glycated hemoglobin [HbA1c], -0.013% HbA1c/250 kcal substitution). In GDI meta-analyses, a common African ancestry-enriched variant (rs79762542) reached study-wide significance and replicated in the UK Biobank cohort, indicating a negative carbohydrate-HbA1c association among major allele homozygotes only. Simulations revealed that >150,000 samples may be necessary to identify similar macronutrient GDIs under realistic assumptions about effect size and measurement error. These results generate hypotheses for further exploration of modifiable metabolic disease risk in additional cohorts with African ancestry. Article highlights: We aimed to identify genetic modifiers of the dietary macronutrient-glycemia relationship using whole-genome sequence data from 10 Trans-Omics for Precision Medicine program cohorts. Substitution models indicated a modest reduction in glycemia associated with an increase in dietary carbohydrate at the expense of fat. Genome-wide interaction analysis identified one African ancestry-enriched variant near the FRAS1 gene that may interact with macronutrient intake to influence hemoglobin A1c. Simulation-based power calculations accounting for measurement error suggested that substantially larger sample sizes may be necessary to discover further gene-macronutrient interactions.Item Physical activity and risk of benign proliferative epithelial disorders of the breast, in the Women's Health Initiative(Oxford University Press, 2022) Peila, Rita; Chlebowski, Rowan T.; Ballinger, Tarah J.; Kamensky, Victor; Richey, Phyllis A.; Saquib, Nazmus; Shadyab, Aladdin H.; Wassertheil-Smoller, Sylvia; Rohan, Thomas E.; Medicine, School of MedicineBackground: Recreational physical activity (PA) has been shown to be inversely associated with breast cancer risk. However, the association of recreational PA with benign proliferative epithelial disorders (BPED) of the breast, conditions associated with increased risk of breast cancer, has not been adequately studied. Methods: We used data from an ancillary study of benign breast disease conducted among the 68 132 postmenopausal women (aged 50-79 at recruitment) participating in the Women's Health Initiative randomized clinical trials. All clinical trial participants underwent annual or biennial mammogram screening. During the follow-up, for women who reported breast biopsies but were cancer free, the associated histological sections were obtained and subjected to standardized central pathology review. Self-reported recreational PA at baseline (n = 61 684) and at 3 years of the follow-up (n = 55 923) were quantified as metabolic equivalents [MET]-h/week. There were 1624 confirmed BPED cases during an average follow-up time of 7.7 years. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Higher average PA over 4 years was associated with lower risk of non-atypical BPED (P-trend = 0.02). There was a 6% lower risk of non-atypical BPED for every 5 MET-h/week increase between baseline and year 3 (HR = 0.94, 95% CI 0.89-0.99). Compared with women who remained inactive (PAbaseline and PAyear3 <9 MET-h/week), those who became active (PAbaseline<9 MET-h/week to PAyear3 ≥9 MET-h/weekee), remained active (PAbaseline and PAyear3 ≥9 MET-h/week), or decreased activity (PAbaseline ≥9 MET-h/week to PAyear3 <9 MET-h/week) had lower BPED risk. Conclusions: Recreational physical activity after menopause was associated with lower BPED risk among postmenopausal women.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 Race-specific associations of 25-hydroxyvitamin D and parathyroid hormone with cardiometabolic biomarkers among US white and black postmenopausal women(Elsevier, 2020-08-01) Xia, Jin; Tu, Wanzhu; Manson, JoAnn E.; Nan, Hongmei; Shadyab, Aladdin H.; Bea, Jennifer W.; Cheng, Ting-Yuan D.; Hou, Lifang; Song, Yiqing; Epidemiology, School of Public HealthBackground: Concentrations of 25-hydroxyvitamin D [25(OH)D] tend to be lower in African Americans than in non-Hispanic whites, but whether adding information on parathyroid hormone (PTH) can help explain the higher cardiometabolic risk among African Americans is unknown. Objectives: This study examined race (black/white)-specific independent and joint associations of 25(OH)D and PTH with cardiometabolic biomarkers including high-sensitivity C-reactive protein (hs-CRP), estimated glomerular filtration rate (eGFR), and homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-B). Methods: Among 1500 white and 1300 black postmenopausal women without cardiovascular disease from the Women's Health Initiative Observational Study, a weighted linear regression analysis and a novel penalized spline-based semiparametric model with contour plots, accounting for possible nonlinear relations and interactions simultaneously, were used to investigate the race-specific independent and joint associations of 25(OH)D and PTH with each biomarker. Results: Black women had lower concentrations of 25(OH)D and higher PTH, HOMA-IR, HOMA-B, hs-CRP, and eGFR than white women (all P values < 0.0001). Lower 25(OH)D and higher PTH were each independently and jointly associated with higher HOMA-IR in both white and black women, whereas a similar joint relation with HOMA-B was observed in white women only. In contrast, PTH was nonlinearly associated with HOMA-B in black women and positively associated with hs-CRP in white women, independently of 25(OH)D. Whereas there was an inverse linear relation between PTH and eGFR in white women after accounting for 25(OH)D, PTH and 25(OH)D were jointly and nonlinearly associated with eGFR in black women. Conclusions: We found that the joint association of 25(OH)D and PTH with β-cell function, systemic inflammation, and kidney function apparently differed between white and black women. Further studies are needed to determine whether differences in the vitamin D-PTH endocrine system contribute to racial disparities in cardiovascular health.Item When the At-Risk Do Not Develop Heart Failure: Understanding Positive Deviance Among Postmenopausal African-American and Hispanic Women(Elsevier, 2021) Breathett, Khadijah; Kohler, Lindsay N.; Eaton, Charles B.; Franceschini, Nora; Garcia, Lorena; Klein, Liviu; Martin, Lisa W.; Ochs-Balcom, Heather M.; Shadyab, Aladdin H.; Cené, Crystal W.; Medicine, School of MedicineBackground: African American and Hispanic postmenopausal women have the highest risk for heart failure compared with other races, but heart failure prevalence is lower than expected in some national cohorts. It is unknown whether psychosocial factors are associated with lower risk of incident heart failure hospitalization among high-risk postmenopausal minority women. Methods and results: Using the Women's Health Initiative Study, African American and US Hispanic women were classified as high-risk for incident heart failure hospitalization with 1 or more traditional heart failure risk factors and the highest tertile heart failure genetic risk scores. Positive psychosocial factors (optimism, social support, religion) and negative psychosocial factors (living alone, social strain, depressive symptoms) were measured using validated survey instruments at baseline. Adjusted subdistribution hazard ratios of developing heart failure hospitalization were determined with death as a competing risk. Positive deviance indicated not developing incident heart failure hospitalization with 1 or more risk factors and the highest tertile for genetic risk. Among 7986 African American women (mean follow-up of 16 years), 27.0% demonstrated positive deviance. Among high-risk African American women, optimism was associated with modestly reduced risk of heart failure hospitalization (subdistribution hazard ratio 0.94, 95% confidence interval 0.91-0.99), and social strain was associated with modestly increased risk of heart failure hospitalization (subdistribution hazard ratio 1.07, 95% confidence interval 1.02-1.12) in the initial models; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses. Among 3341 Hispanic women, 25.1% demonstrated positive deviance. Among high-risk Hispanic women, living alone was associated with increased risk of heart failure hospitalization (subdistribution hazard ratio 1.97, 95% confidence interval 1.06-3.63) in unadjusted analyses; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses. Conclusions: Among postmenopausal African American and Hispanic women, a significant proportion remained free from heart failure hospitalization despite having the highest genetic risk profile and 1 or more traditional risk factors. No observed psychosocial factors were associated with incident heart failure hospitalization in high-risk African Americans and Hispanics. Additional investigation is needed to understand protective factors among high-risk African American and Hispanic women.