Admixture Mapping of 15,280 African Americans Identifies Obesity Susceptibility Loci on Chromosomes 5 and X

The prevalence of obesity (body mass index (BMI) ≥30 kg/m2) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (ρ = −0.042, P = 1.6×10−7). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = −3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = −4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI

Association of Arterial Stiffness and Central Pressure With Cognitive Function in Incident Hemodialysis Patients: The PACE Study

Cognitive impairment commonly occurs in hemodialysis patients, with vascular disease potentially implicated in its pathogenesis. However, the relationship of detailed vascular assessment with cognitive function in patients new to hemodialysis has not been demonstrated. Methods: In a prospective study of incident hemodialysis participants enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in ESRD (PACE) study, we determined aortic stiffness by pulse-wave velocity (PWV), systemic arterial stiffness by the augmentation index (AIx) and central pulse pressure (cPP), and examined their associations with cognitive processing speed, executive function, and global cognitive impairment measured by the Trail making test A (TMTA), Trail making test B (TMTB), and the modified Mini-Mental State Exam (3MS). Results: Mean baseline age was 55 ± 13 years, 58% were male, 72% were African American, 35% had coronary artery disease, 55% had diabetes, and 10% had cognitive impairment. At baseline, higher PWV and cPP were associated with a longer TMTA, and a higher PWV was associated with a longer TMTB, but the associations were attenuated after multivariable adjustment. At 1 year, PWV was not independently associated with TMTA, TMTB, or 3MS. However, unadjusted and adjusted analyses revealed every 10% increase in AIx and 10 mm Hg increase in cPP were associated with longer TMTB (time differenceAIx: 0.14; 95% confidence interval [CI]: 0.02−0.25 log-seconds; time differencecPP: 0.11; 95% CI: 0.05−0.17 log-seconds) and global cognitive impairment (odds ratio [OR]AIx: 10.23; 95% CI: 1.77−59.00; ORcPP: 2.88; 95% CI: 1.48−5.59). Discussion: Higher AIx and cPP, which are indicative of abnormal wave reflections in distal vessels, are associated with, and might contribute to, declining cognitive function in patients starting hemodialysis

Obstructive Sleep Apnea Increases Sudden Cardiac Death in Incident Hemodialysis Patients

BACKGROUND:Mortality in end-stage renal disease (ESRD) occurs predominantly from cardiovascular disease (CVD) and sudden cardiac death (SCD). Obstructive sleep apnea (OSA) is characterized by periodic airflow limitation associated with sleep arousal and oxygen desaturation and is prevalent in patients with ESRD. Whether OSA increases the risk for SCD, cardiovascular and all-cause mortality among hemodialysis patients remains unknown. METHODS:In a prospective cohort of 558 incident hemodialysis patients, we examined the association of OSA with all-cause mortality, cardiovascular mortality, and SCD using Cox proportional hazards models controlling for traditional CVD risk factors. RESULTS:Sixty-six incident hemodialysis patients (12%) had OSA. Mean age (56 years) and percentage of males (56%) were identical in OSA and no-OSA groups. Fewer African Americans had OSA than non-African Americans (9 vs. 18%, respectively). Participants with OSA had higher body-mass index, Charlson comorbidity score, and left ventricular mass index and greater prevalence of diabetes and coronary artery disease. During 1,080 person-years of follow-up, 104 deaths occurred, 29% of which were cardiovascular. OSA was associated with a higher risk of all-cause mortality (HR 1.90 [95% CI 1.04-3.46]) and cardiovascular mortality (HR 3.62 [95% CI 1.36-9.66]) after adjusting for demographics and body-mass index. OSA was associated with a higher risk of SCD after adjusting for demographics (HR 3.28 [95% CI 1.12-9.57]) and multiple cardiovascular risk factors. CONCLUSIONS:Incident hemodialysis patients with OSA are at increased risk of all-cause and cardiovascular mortality and SCD. Future studies should assess the impact of screening for OSA and OSA-targeted interventions on mortality in ESRD