77 research outputs found
New genetic loci link adipose and insulin biology to body fat distribution.
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
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A Prospective Study of the Relationship Over Time of Behavior Problems, Intellectual Functioning, and Family Functioning in Children With Sickle Cell Disease: A Report From the Cooperative Study of Sickle Cell Disease
Objective To longitudinally assess the relationship of behavioral problems, intellectual functioning, and family functioning in children with sickle cell disease (SCD). Method The study sample included 222 children enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD). The study protocol included intellectual evaluation and brain magnetic resonance imaging (MRI) of the children, and mothers completed the Child Behavior Checklist and Family Environment Scale. At least two complete sets of measures were obtained across four assessment points over the study period of 9 years. Results Intellectual functioning declined, but family functioning and behavior problem scores did not change significantly. Consistent behavior problems were reported by mothers for 9% of the children. The risk of consistent behavior problems was not related to MRI classification, gender, education level of mother, or age of the child but significantly increased with higher baseline levels of family conflict and decreased with higher baseline full-scale IQ. An increase in behavior problems was associated with an increase in family conflict. Conclusions Maternal appraisal of family conflict is a risk factor for the small subgroup of children with SCD with consistent mother-reported behavior problems and a salient intervention target for fostering adaptation
Silent cerebral infarcts in very young children with sickle cell anaemia are associated with a higher risk of stroke
Silent cerebral infarctions (SCI) are the most common neurological injury in children with sickle cell anaemia (SCA), but their incidence/prognosis in early childhood has not been well described. We report clinical, neuroradiological, psychometric and academic follow-up over an average period of 14 years in 37 children with SCA who had magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the brain between ages 7 and 48 months. Ten patients (27%) younger than age 5 years (Group I) had SCI, as did 12 (32%) older than 5 years (Group II). Fifteen (41%) had no lesions (Group III). Overt stroke or transient ischaemic attack occurred in 5/9 (56%) in Group I. Most Group I patients had progressive MRI abnormalities, concurrent stenosis, decreased cognitive ability, attention/executive function deficits and hindered academic attainment. The proportions of subjects in Group I with subsequent neurological events (P ≤ 0·006), progressive ischaemia (P ≤ 0·001) and vascular stenosis (P ≤ 0·006) were greater than in Groups II and III. Thus, SCI in young children with SCA may predict overt central nervous system events, progressive MRI abnormalities, stenosis, cognitive dysfunction and poor academic performance. Children younger than 5 years may benefit from MRI/MRA testing and should be considered for aggressive intervention when SCI are detected
Protection from sickle cell retinopathy is associated with elevated HbF levels and hydroxycarbamide use in children
Elevated foetal haemoglobin (HbF) levels are protective against some manifestations of sickle cell anaemia but the impact on retinopathy is unknown. We report on 123 children with HbSS, 10·6% of whom developed retinopathy. Independent of hydroxycarbamide, children with a HbF \u3c15% had 7·1-fold (95% confidence interval, 1·5-33·6) higher odds of developing retinopathy. In children treated with hydroxycarbamide, those with retinopathy had lower HbF levels compared to children without retinopathy (9% vs. 16%; P = 0·005). We report a protective benefit of elevated HbF regarding retinopathy, and our data suggests induction of HbF with hydroxycarbamide may prevent retinopathy in children. © 2013 Blackwell Publishing Ltd
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