Background Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain. Objective Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type-2 diabetes (T2D), coronary heart disease (CHD), ischemic stroke and heart failure. Methods We investigated 28 SNPs known to regulate serum urate levels in association with a range of vascular and non-vascular risk factors to assess pleiotropy. To limit genetic confounding, 14 SNPs found exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2D (26,488/83,964), CHD (54,501/68,275), ischemic stroke (14,779/67,312) and heart failure (4,526/18,400). As a positive control, we also investigated our genetic instrument in 3,151 gout cases and 68,350 controls. Results Serum urate levels, raised by 1 standard deviation (SD) due to the genetic score, were not associated with T2D (odds ratio [OR] 0.95, 95% CI, 0.86–1.05), CHD (OR. 1.02, 95% CI, 0.92–1.12), ischemic stroke (OR. 0.99, 95% CI, 0.88–1.12), or heart failure (OR. Q1.07, 95% CI, 0.88–1.30). These results were in contrast with previous prospective studies that observed increased risks of T2D (OR. 1.25, 95% CI, 1.13–1.37), CHD (OR. 1.06, 95% CI, 1.03–1.09), ischemic stroke (OR. 1.17, 95% CI, 1.00–1.37), and heart failure (OR. 1.19, 95% CI, 1.17–1.21) for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (OR. 5.84, 95% CI, 4.56–7.49), which was directionally consistent with associations observed in previous epidemiological studies Conclusions Evidence from this study does not support a causal role of circulating serum urate levels in T2D, CHD, ischemic stroke, or heart failure. Lowering serum urate levels may not translate into risk reductions for cardiometabolic conditions.
BackgroundMultiple genetic variants have been reliably associated with obesity-related traits in Europeans, but little is known about their associations and interactions with lifestyle factors in South Asians.MethodsIn 16,157 Pakistani adults (8232 controls; 7925 diagnosed with myocardial infarction [MI]) enrolled in the PROMIS Study, we tested whether: a) BMI-associated loci, individually or in aggregate (as a genetic risk score - GRS), are associated with BMI; b) physical activity and smoking modify the association of these loci with BMI. Analyses were adjusted for age, age2, sex, MI (yes/no), and population substructure.ResultsOf 95 SNPs studied here, 73 showed directionally consistent effects on BMI as reported in Europeans. Each additional BMI-raising allele of the GRS was associated with 0.04 (SE = 0.01) kg/m2 higher BMI (P = 4.5 × 10−14). We observed nominal evidence of interactions of CLIP1 rs11583200 (Pinteraction = 0.014), CADM2 rs13078960 (Pinteraction = 0.037) and GALNT10 rs7715256 (Pinteraction = 0.048) with physical activity, and PTBP2 rs11165643 (Pinteraction = 0.045), HIP1 rs1167827 (Pinteraction = 0.015), C6orf106 rs205262 (Pinteraction = 0.032) and GRID1 rs7899106 (Pinteraction = 0.043) with smoking on BMI.ConclusionsMost BMI-associated loci have directionally consistent effects on BMI in Pakistanis and Europeans. There were suggestive interactions of established BMI-related SNPs with smoking or physical activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-015-0259-x) contains supplementary material, which is available to authorized users.
In summary, we have identified a novel interaction between smoking and variation at the FLJ33534 locus in relation to BMI in people from Pakistan.
Objective The Asian American population in the U.S. comprises various, ethnically diverse subgroups. Traditionally, this population has been studied as a single, aggregated group, potentially masking differences in risk among subgroups. Analyses using disaggregated data can help better characterize the health needs of different Asian subpopulations and inform targeted, effective public health interventions. We assessed the prevalence of cardiovascular disease (CVD) risk factors and atherosclerotic CVD (ASCVD) and their associations with socioeconomic factors among Chinese, Asian Indian, Filipino and Other Asian subjects, compared with non-Hispanic White (NHW) subjects in the U.S. Methods : Cross-sectional study using data from 298,286 adults from the National Health Interview Survey (NHIS) from 2007 to 2018. We utilized chi-squared tests to compare characteristics across subgroups. Weighted proportions and unadjusted and adjusted logistic regression models were utilized to examine the associations between Asian subgroups, self-reported CVD risk factors and self-reported ASCVD, as well as between socioeconomic factors within each Asian subgroup. Results : Asian Indian subjects had the highest prevalence of diabetes (12.5%), while Filipino subjects had the highest prevalence of hyperlipidemia (27.7%), hypertension (29.8%) and obesity (19.8%). Despite this, the prevalence of self-reported ASCVD was lower in all Asian groups compared with NHWs. Chinese subjects had the lowest odds of having each of the CVD risk factors assessed. Conclusion : We found considerable heterogeneity in the distribution of risk factors as well as ASCVD among Asian subgroups in the US. Compared with health system or community-based reports, the prevalence of risk factors and ASCVD may be underestimated in some Asian NHIS subgroups. There is an urgent need for efforts to improve recruitment of Asian participants of heterogeneous socioeconomic backgrounds in national surveys, as well as to perform a thorough assessment of risk factors and disease in this population, not relying solely on self-report.
RESEARCH• Assesses knowledge and attitudes of a dental team about domestic violence before and after a brief training intervention.• Post-training there was improved recognition about the dental team's role in the healthcare response to domestic violence.• Brief training can improve dental staff comfort asking patients about abuse, though whether false confi dence in dealing with abused patients results needs to be established.• We suggest that brief training be complemented with in depth practical training and the development of appropriate processes for dealing with abuse victims. I N B R I E FChanges in the levels of knowledge and attitudes of dental hospital staff about domestic violence following attendance at an awareness raising seminar A. L. Warburton, 1 B. Hanif, 2 C. Rowsell 3 and P. Coulthard 4Objectives To assess changes in dental team knowledge and awareness about domestic violence following attendance at a brief training intervention. Materials and methods Seventy-fi ve dental hospital staff at the University of Manchester Dental Hospital attended a two-hour session delivered by Manchester's City Wide NHS Domestic Violence Project manager. Participants completed identical questionnaires immediately before and after the session. Paired t-tests were conducted to determine changes in responses to individual questions before and after training. Independent sample t-tests were also conducted to compare mean responses by sex. Results Statistically signifi cant improvements were seen in 50% of attitude questions and 100% of knowledge questions. After training, there was improved recognition that interpersonal violence was a health issue and that the dental profession should be more involved in identifi cation of abuse. There was also improved comfort asking about abuse and respondents were less afraid of offending the patient and less likely to blame the victims for being abused. Statistically signifi cant sex differences at baseline were also seen for several items: females obtaining more correct answers at baseline than males. Conclusions Brief domestic violence training interventions can be effective in improving knowledge and attitudes amongst a dental team but could lead to false confi dence in staff and should be followed by in-depth practical training and the development of appropriate processes for dealing with abuse victims.
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