Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention

Prevalence of Homelessness by Gender in an Emergency Department Population in Pennsylvania.

Context: According to the US Department of Housing and Urban Development, nearly 1.5 million people spend at least 1 night in an emergency shelter or transitional housing each year, and more than 500,000 people are homeless on a given night in the United States. To our knowledge, limited data exist regarding the prevalence of homelessness in ED patients by gender (male, female, and transgender). Objective: To assess the prevalence of homelessness by gender in 3 EDs in Pennsylvania. Methods: From May 2015 through February 2016, patients in 3 EDs were approached to take a 5-question homelessness screening survey. To participate, patients had to be aged at least 18 years, speak English, have capacity to complete the survey, be willing to participate, and not be critically ill. Frequency comparisons were made using χ2 analysis. Statistical significance was defined as P≤.05. Results: A total of 4395 patients were included in the analysis. The mean (SD) age of the participants was 50.8 (20.5) years; 2557 (58.2%) were women and 3 (0.07%) were transgender. No difference in the rate of homelessness was observed between men and women, with 135 of 1835 men (7.4%) and 173 of 2557 women (6.8%) screening positive for homelessness (P=.472). Forty of 2557 women (1.6%) and 41 of 1835 men (2.2%) admitted they had slept outside or in an abandoned building, their car, an emergency shelter, or a hotel due to financial hardship in the past 60 days (P=.26). One transgender patient screened positive for homelessness. The mean age of participants who screened positive for homelessness was 40.9 (15.9) years. Conclusion: No significant difference was observed in the rate of homelessness between men and women in this ED population, which defies the perception that this issue primarily affects men. Public health interventions aimed at homeless populations should consider that both men and women may be equally affected by homelessness

Lack of Gender Differences in Prevalence of Homelessness in the Emergency Department.

Background: Concordant with the NIH policy on the inclusion of women in clinical research, and their support of analyses that address potential sex and gender differences, researchers are focusing more on assessing outcomes by sex. Objective(s): We set out to assess gender differences in the prevalence of homelessness in the Emergency Department (ED). Material/Methods: From 5/2015-2/2016, ED patients were approached to take a five-question homelessness screening survey. To participate, patients had to be: 18 years or older, speak English, have capacity, not be critically ill, and be willing to participate. Results: 4494 subjects met inclusion criteria; 99 surveys were excluded (took the survey before). 4395 subjects were analyzed. The mean age of subjects was 50.8 years (SD 20.5) and 2,557 (58.2%) were women. No difference in the rate of homelessness was observed between male and female participants with 135 men out of 1,835 (7.4%) and 173 out of 2,557 (6.8%) women screening positive, (p = 0.472). The mean age of those screening positive for homelessness was 40.9 years (SD 15.9); the mean age of men screening positive was 42.4 years (SD = 16.2) and women was 43.7 years (SD 16.9). Both men (N = 41) and women (N = 40) admitted they had slept outside, in an abandoned building, in their car, a shelter or a motel due to financial hardship. Conclusions: We did not observe differences in the rate of homelessness between men and women who screened positive for homelessness in the ED. These data combat stereotypes that this social issue is a problem primarily affecting male populations. Public health interventions aimed at homeless populations should be cognizant that both genders are dealing with this burden. A deeper understanding of the demographics of homelessness may allow for better access to medical treatment since women have different health care needs than men

Low thyroid function is not associated with an accelerated deterioration in renal function

Background: Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups. Methods: Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models. Results: A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) −4.07 (−6.37 to −1.78) and −2.40 (−3.78 to −1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50–4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function. Conclusions: Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations

Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity

Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10 -7, range P = 9.2 × 10 -8 to 6.0 × 10 -46; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10 -6, range P = 5.5 × 10 -6 to 6.1 × 10 -35, n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10 -54). Our results provide new insights into the biologic pathways influen

Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity

Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10(-7), range P = 9.2 × 10(-8) to 6.0 × 10(-46); n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10(-6), range P = 5.5 × 10(-6) to 6.1 × 10(-35), n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10(-54)). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity

Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity

Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances1,2. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation3,4,5,6, a key regulator of gene expression and molecular phenotype7. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10−7, range P = 9.2 × 10−8 to 6.0 × 10−46; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10−6, range P = 5.5 × 10−6 to 6.1 × 10−35, n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07–2.56); P = 1.1 × 10−54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity