Polygenic risk scores (PRSs) are weighted sums of risk allele counts of single‐nucleotide polymorphisms (SNPs) associated with a disease or trait. PRSs are typically constructed based on published ...results from Genome‐Wide Association Studies (GWASs), and the majority of which has been performed in large populations of European ancestry (EA) individuals. Although many genotype‐trait associations have generalized across populations, the optimal choice of SNPs and weights for PRSs may differ between populations due to different linkage disequilibrium (LD) and allele frequency patterns. We compare various approaches for PRS construction, using GWAS results from both large EA studies and a smaller study in Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL,
n
=
12
,
803). We consider multiple approaches for selecting SNPs and for computing SNP weights. We study the performance of the resulting PRSs in an independent study of Hispanics/Latinos from the Women’s Health Initiative (WHI,
n
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3
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582). We support our investigation with simulation studies of potential genetic architectures in a single locus. We observed that selecting variants based on EA GWASs generally performs well, except for blood pressure trait. However, the use of EA GWASs for weight estimation was suboptimal. Using non‐EA GWAS results to estimate weights improved results.
Abstract
We sought to assess the relationship between sleep duration, sleep disturbance, and leukemia incidence among postmenopausal women. This study included 130,343 postmenopausal women aged 50–79 ...years who were enrolled in the Women’s Health Initiative (WHI) during 1993–1998. Information on self-reported typical sleep duration and sleep disturbance was obtained by questionnaire at baseline, and sleep disturbance level was defined according to the Women’s Health Initiative Insomnia Rating Scale (WHIIRS). WHIIRS scores of 0–4, 5–8, and 9–20 comprised 37.0%, 32.6%, and 30.4% of all women, respectively. After an average of 16.4 years (2,135,109 cumulative person-years) of follow-up, 930 of the participants were identified as having incident leukemia. Compared with women with the lowest level of sleep disturbance (WHIIRS score 0–4), women with higher sleep disturbance levels (WHIIRS scores of 5–8 and 9–20) had 22% (95% confidence interval (CI): 1.04, 1.43) and 18% (95% CI: 1.00, 1.40) excess risks of leukemia, respectively, after multivariable adjustment. A significant dose-response trend was found for the association between sleep disturbance and leukemia risk (P for trend = 0.048). In addition, women with the highest level of sleep disturbance had a higher risk of myeloid leukemia (for WHIIRS score 9–20 vs. WHIIRS score 0–4, hazard ratio = 1.39, CI: 1.05, 1.83). Higher sleep disturbance level was associated with increased risk of leukemia, especially for myeloid leukemia among postmenopausal women.
There is growing recognition that reproductive factors are associated with increased risk of future cardiovascular disease. Infertility has been less well studied, although emerging data support its ...association with increased risk of cardiovascular disease. Whether infertility is associated with future risk of heart failure (HF) is not known.
This study sought to examine the development of HF and HF subtypes in women with and without history of infertility.
We followed postmenopausal women from the Women’s Health Initiative prospectively for the development of HF. Infertility was self-reported at study baseline. Multivariable cause-specific Cox models were used to evaluate the association of infertility with incident overall HF and HF subtypes (heart failure with preserved ejection fraction HFpEF: left ventricular ejection fraction of ≥50% vs heart failure with reduced ejection fraction HFrEF: left ventricular ejection fraction of <50%).
Among 38,528 postmenopausal women (mean age: 63 ± 7 years), 5,399 (14%) participants reported a history of infertility. Over a median follow-up of 15 years, 2,373 developed incident HF, including 807 with HFrEF and 1,133 with HFpEF. Infertility was independently associated with future risk of overall HF (HR: 1.16; 95% CI: 1.04-1.30; P = 0.006). Notably, when examining HF subtypes, infertility was associated with future risk of HFpEF (HR: 1.27; 95% CI: 1.09-1.48; P = 0.002) but not HFrEF (HR: 0.97; 95% CI: 0.80-1.18).
Infertility was significantly associated with incident HF. This was driven by increased risk of HFpEF, but not HFrEF, and appeared independent of traditional cardiovascular risk factors and other infertility-related conditions. Future research should investigate mechanisms that underlie the link between infertility and HFpEF.
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To assess the associations among several anthropometric measures, as well as BMI trajectories and colorectal cancer (CRC) risk in older women.
Prospective cohort study.
Forty clinical centres in the ...USA.
Totally, 79 034 postmenopausal women in the Women's Health Initiative Observational Study.
During an average of 15·8 years of follow-up, 1514 CRC cases were ascertained. Five BMI trajectories over 18-50 years of age were identified using growth mixture model. Compared with women who had a normal BMI at age 18, women with obesity at age 18 had a higher risk of CRC (HR 1·58, 95 % CI 1·02, 2·44). Compared with women who kept relatively low normal body size during adulthood, women who progressed from normal to obesity (HR 1·29, 95 % CI 1·09, 1·53) and women who progressed from overweight to obesity (HR 1·37, 95 % CI 1·13, 1·68) had higher CRC risks. A weight gain > 15 kg from age 18 to 50 (HR 1·20, 95 % CI 1·04, 1·40) and baseline waist circumference > 88 cm (HR 1·33, 95 % CI 1·19, 1·49) were associated with higher CRC risks, compared with stable weight and waist circumference ≤ 88 cm, respectively.
Women who have a normal weight in early adult life and gain substantial weight later, as well as those who are persistently heavy over adulthood, demonstrated a higher risk of developing CRC. Our study highlights the importance of maintaining a healthy body weight over the life course for reducing the risk of developing CRC in women.
Abstract
Aims
Central adiposity is associated with increased cardiovascular disease (CVD) risk, even among people with normal body mass index (BMI). We tested the hypothesis that regional body fat ...deposits (trunk or leg fat) are associated with altered risk of CVD among postmenopausal women with normal BMI.
Methods and results
We included 2683 postmenopausal women with normal BMI (18.5 to <25 kg/m2) who participated in the Women’s Health Initiative and had no known CVD at baseline. Body composition was determined by dual energy X-ray absorptiometry. Incident CVD events including coronary heart disease and stroke were ascertained through February 2017. During a median 17.9 years of follow-up, 291 incident CVD cases occurred. After adjustment for demographic, lifestyle, and clinical risk factors, neither whole-body fat mass nor fat percentage was associated with CVD risk. Higher percent trunk fat was associated with increased risk of CVD highest vs. lowest quartile hazard ratio (HR) = 1.91, 95% confidence interval (CI) 1.33–2.74; P-trend <0.001, whereas higher percent leg fat was associated with decreased risk of CVD (highest vs. lowest quartile HR = 0.62, 95% CI 0.43–0.89; P-trend = 0.008). The association for trunk fat was attenuated yet remained significant after further adjustment for waist circumference or waist-to-hip ratio. Higher percent trunk fat combined with lower percent leg fat was associated with particularly high risk of CVD (HR comparing extreme groups = 3.33, 95% CI 1.46–7.62).
Conclusion
Among postmenopausal women with normal BMI, both elevated trunk fat and reduced leg fat are associated with increased risk of CVD.
Highlights • Recent studies confirm the association of APOE with longevity. • Mutations in mitochondrial DNA may be linked to longevity. • Longevity may be influenced by joint effects of multiple ...genetic variants. • Association of genetic factors with healthy aging remains poorly defined.
Background
Research has suggested optimism is associated with healthy aging and exceptional longevity, but most studies were conducted among non‐Hispanic White populations. We examined associations ...of optimism to longevity across racial and ethnic groups and assessed healthy lifestyle as a possible mediating pathway.
Methods
Participants from the Women's Health Initiative (N = 159,255) completed a validated measure of optimism and provided other demographic and health data at baseline. We evaluated associations of optimism with increments in lifespan using accelerated failure time models, and with likelihood of exceptional longevity (survival to age ≥90) using Poisson regression models. Causal mediation analysis explored whether lifestyle‐related factors mediated optimism‐lifespan associations.
Results
After covariate adjustment, the highest versus lowest optimism quartile was associated with 5.4% (95% confidence interval CI = 4.5, 6.4%) longer lifespan. Within racial and ethnic subgroups, these estimates were 5.1% (95%CI = 4.0, 6.1%) in non‐Hispanic White, 7.6% (95%CI = 3.6, 11.7%) in Black, 5.4% (95%CI = −0.1, 11.2%) in Hispanic/Latina, and 1.5% (95% CI = −5.0, 8.5) in Asian women. A high proportion (53%) of the women achieved exceptional longevity. Participants in the highest versus lowest optimism quartile had greater likelihood of achieving exceptional longevity (e.g., full sample risk ratio = 1.1, 95%CI = 1.1, 1.1). Lifestyle mediated 24% of the optimism‐lifespan association in the full sample, 25% in non‐Hispanic White, 10% in Black, 24% in Hispanic/Latina, and 43% in Asian women.
Conclusions
Higher optimism was associated with longer lifespan and a greater likelihood of achieving exceptional longevity overall and across racial and ethnic groups. The contribution of lifestyle to these associations was modest. Optimism may promote health and longevity in diverse racial and ethnic groups. Future research should investigate these associations in less long‐lived populations.
See related Editorial by Cobert et al. and article by Jeffrey M. Levine in this issue.
Background Dietary recommendations regarding protein intake have been focused on the amount of protein. However, such recommendations without considering specific protein sources may be simplistic ...and insufficient. Methods and Results We included 102 521 postmenopausal women enrolled in the Women's Health Initiative between 1993 and 1998, and followed them through February 2017. During 1 876 205 person-years of follow-up, 25 976 deaths occurred. Comparing the highest with the lowest quintile, plant protein intake was inversely associated with all-cause mortality (hazard ratio HR, 0.91 0.86, 0.96), cardiovascular disease mortality (HR, 0.88 0.79, 0.97), and dementia mortality (HR, 0.79 0.67, 0.94). Among major protein sources, comparing the highest with the lowest quintile of consumption, processed red meat (HR, 1.06 1.01, 1.10) or eggs (HR, 1.14 1.10, 1.19) was associated with higher risk of all-cause mortality. Unprocessed red meat (HR, 1.12 1.02, 1.23), eggs (HR, 1.24 1.14, 1.34), or dairy products (HR, 1.11 1.02, 1.22) was associated with higher risk of cardiovascular disease mortality. Egg consumption was associated with higher risk of cancer mortality (HR, 1.10 1.02, 1.19). Processed red meat consumption was associated with higher risk of dementia mortality (HR, 1.20 1.05, 1.32), while consumption of poultry (HR, 0.85 0.75, 0.97) or eggs (HR, 0.86 0.75, 0.98) was associated with lower risk of dementia mortality. In substitution analysis, substituting of animal protein with plant protein was associated with a lower risk of all-cause mortality, cardiovascular disease mortality, and dementia mortality, and substitution of total red meat, eggs, or dairy products with nuts was associated with a lower risk of all-cause mortality. Conclusions Different dietary protein sources have varying associations with all-cause mortality, cardiovascular disease mortality, and dementia mortality. Our findings support the need for consideration of protein sources in future dietary guidelines.
To examine the association between manganese intake and the risk of type 2 diabetes in postmenopausal women and determine whether this association is mediated by circulating markers of inflammation.
...We included 84,285 postmenopausal women without a history of diabetes from the national Women's Health Initiative Observational Study (WHI-OS). Replication analysis was then conducted among 62,338 women who participated in the WHI-Clinical Trial (WHI-CT). Additionally, data from a case-control study of 3,749 women nested in the WHI-OS with information on biomarkers of inflammation and endothelial dysfunction were examined using mediation analysis to determine the relative contributions of these known biomarkers by which manganese affects type 2 diabetes risk.
Compared with the lowest quintile of energy-adjusted dietary manganese, WHI-OS participants in the highest quintile had a 30% lower risk of type 2 diabetes (hazard ratio HR 0.70 95% CI 0.65, 0.76). A consistent association was also confirmed in the WHI-CT (HR 0.79 95% CI 0.73, 0.85). In the nested case-control study, higher energy-adjusted dietary manganese was associated with lower circulating levels of inflammatory biomarkers that significantly mediated the association between dietary manganese and type 2 diabetes risk. Specifically, 19% and 12% of type 2 diabetes risk due to manganese were mediated through interleukin 6 and hs-CRP, respectively.
Higher intake of manganese was directly associated with a lower type 2 diabetes risk independent of known risk factors. This association may be partially mediated by inflammatory biomarkers.
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