Self-Regulation of Emotion, Functional Impairment, and Comorbidity Among Children With AD/HD

Objective: This study investigated the role of self-regulation of emotion in relation to functional impairment and comorbidity among children with and without AD/HD. Method: A total of 358 probands and their siblings participated in the study, with 74% of the sample participants affected by AD/HD. Parent-rated levels of emotional lability served as a marker for self-regulation of emotion. Results: Nearly half of the children affected by AD/HD displayed significantly elevated levels of emotional lability versus 15% of those without this disorder. Children with AD/HD also displayed significantly higher rates of functional impairment, comorbidity, and treatment service utilization. Emotional lability partially mediated the association between AD/HD status and these outcomes. Conclusion: Findings lent support to the notion that deficits in the self-regulation of emotion are evident in a substantial number of children with AD/HD and that these deficits play an important role in determining functional impairment and comorbidity outcomes

Alloimmunization in sickle cell disease: changing antibody specificities and association with chronic pain and decreased survival: Alloimmunization in SCD

Alloimmunization remains a significant complication of transfusion and has been associated with multiple factors, including inflammation, an important pathophysiologic mechanism in sickle cell disease (SCD). We explored whether alloimmunization is associated with disease severity in SCD

Factors associated with survival in a contemporary adult sickle cell disease cohort: Factors Associated with Survival in Sickle Cell Disease

We examined the relationship of clinical differences among sickle cell disease (SCD) patients in order to understand the major contributors to early mortality in a contemporary cohort

Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results

Metabolite genome-wide association studies (mGWAS) have advanced our understanding of the genetic control of metabolite levels. However, interpreting these associations remains challenging due to a lack of tools to annotate gene-metabolite pairs beyond the use of conservative statistical significance threshold. Here, we introduce the shortest reactional distance (SRD) metric, drawing from the comprehensive KEGG database, to enhance the biological interpretation of mGWAS results. We applied this approach to three independent mGWAS, including a case study on sickle cell disease patients. Our analysis reveals an enrichment of small SRD values in reported mGWAS pairs, with SRD values significantly correlating with mGWAS p values, even beyond the standard conservative thresholds. We demonstrate the utility of SRD annotation in identifying potential false negatives and inaccuracies within current metabolic pathway databases. Our findings highlight the SRD metric as an objective, quantitative and easy-to-compute annotation for gene-metabolite pairs, suitable to integrate statistical evidence to biological networks

Discovery and Functional Annotation of SIX6 Variants in Primary Open-Angle Glaucoma

Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) is the most common subtype and is a complex trait with multigenic inheritance. Genome-wide association studies have previously identified a significant association between POAG and the SIX6 locus (rs10483727, odds ratio (OR) = 1.32, p = 3.87×10−11). SIX6 plays a role in ocular development and has been associated with the morphology of the optic nerve. We sequenced the SIX6 coding and regulatory regions in 262 POAG cases and 256 controls and identified six nonsynonymous coding variants, including five rare and one common variant, Asn141His (rs33912345), which was associated significantly with POAG (OR = 1.27, p = 4.2×10−10) in the NEIGHBOR/GLAUGEN datasets. These variants were tested in an in vivo Danio rerio (zebrafish) complementation assay to evaluate ocular metrics such as eye size and optic nerve structure. Five variants, found primarily in POAG cases, were hypomorphic or null, while the sixth variant, found only in controls, was benign. One variant in the SIX6 enhancer increased expression of SIX6 and disrupted its regulation. Finally, to our knowledge for the first time, we have identified a clinical feature in POAG patients that appears to be dependent upon SIX6 genotype: patients who are homozygous for the SIX6 risk allele (His141) have a statistically thinner retinal nerve fiber layer than patients homozygous for the SIX6 non-risk allele (Asn141). Our results, in combination with previous SIX6 work, lead us to hypothesize that SIX6 risk variants disrupt the development of the neural retina, leading to a reduced number of retinal ganglion cells, thereby increasing the risk of glaucoma-associated vision loss

MYH9 and APOL1 are both associated with sickle cell disease nephropathy

Renal failure occurs in 5–18% of sickle cell disease (SCD) patients and is associated with early mortality. At risk SCD patients cannot be identified prior to the appearance of proteinuria and the pathobiology is not well understood. The MYH9 and APOL1 genes have been associated with risk for focal segmental glomerulosclerosis and end-stage renal disease in African Americans