Integrative multiomics analyses of adipose and muscle tissue transcripts, S, and genotypes revealed novel genetic regulatory mechanisms of insulin resistance in African Americans.

Relative to European Americans, type 2 diabetes (T2D) is more prevalent in African Americans (AAs). Genetic variation may modulate transcript abundance in insulin-responsive tissues and contribute to risk; yet published studies identifying expression quantitative trait loci (eQTLs) in African ancestry populations are restricted to blood cells. This study aims to develop a map of genetically regulated transcripts expressed in tissues important for glucose homeostasis in AAs, critical for identifying the genetic etiology of T2D and related traits. Quantitative measures of adipose and muscle gene expression, and genotypic data were integrated in 260 non-diabetic AAs to identify expression regulatory variants. Their roles in genetic susceptibility to T2D, and related metabolic phenotypes were evaluated by mining GWAS datasets. eQTL analysis identified 1,971 and 2,078 cis-eGenes in adipose and muscle, respectively. Cis-eQTLs for 885 transcripts including top cis-eGenes CHURC1, USMG5, and ERAP2, were identified in both tissues. 62.1% of top cis-eSNPs were within ±50kb of transcription start sites and cis-eGenes were enriched for mitochondrial transcripts. Mining GWAS databases revealed association of cis-eSNPs for more than 50 genes with T2D (e.g. PIK3C2A, RBMS1, UFSP1), gluco-metabolic phenotypes, (e.g. INPP5E, SNX17, ERAP2, FN3KRP), and obesity (e.g. POMC, CPEB4). Integration of GWAS meta-analysis data from AA cohorts revealed the most significant association for cis-eSNPs of ATP5SL and MCCC1 genes, with T2D and BMI, respectively. This study developed the first comprehensive map of adipose and muscle tissue eQTLs in AAs (publically accessible at https://mdsetaa.phs.wakehealth.edu) and identified genetically-regulated transcripts for delineating genetic causes of T2D, and related metabolic phenotypes.

The ontogeny of renin mRNA and renin content from renal cortical slices was studied in two groups of ovine fetuses at 92-94 days (0.64 gestation) and at 138-142 days (0.96 gestation), newborn lambs (0.4-2 days old), and adult sheep. Renal renin mRNA was identified by hybridization with a 32P-labeled full length rat renin cDNA. Renal renin content was measured as nanograms of angiotensin I generated per hour (active renin). There was a significant age effect on renin mRNA levels (F = 10.0, P < 0.001); values increase significantly between 0.64 and 0.95 g (P < 0.005), remain elevated in the newborns (P < 0.05), and subsequently decline in adulthood (P < 0.005). Likewise, renal renin content was significantly higher in late gestation fetuses and newborn lambs than in early gestation and adults (F = 8.3, P < 0.003). The renal renin content was strongly correlated with renin mRNA levels (R = 0.88, P < 0.0001). These results suggest that 1) the renin gene is developmentally regulated in the ovine kidney and 2) the renal content of active renin in basal conditions is regulated, at least in part, by events at the transcriptional level.

Caregiver burden—the stress associated with caring for a loved one with chronic illness—is rated as high or very high by about two-thirds of Alzheimer's caregivers. At Wake Forest School of Medicine, both patients with memory loss or cognitive impairment and caregivers are evaluated at a geriatrician-led co-located Memory Assessment Clinic (MAC). In a sample of 100 MAC-evaluated patient-caregiver dyads this study assessed both patient severity of Alzheimer's disease or other dementia, self-reported behavioral disturbances, degree of functional independence in general activities of daily living and instrumental activities of daily living (IADLs), and caregiver stress as measured by the Caregiver Burden Scale (CBS). Several patient factors were found to be related to high caregiver stress (CBS score &gt; 25), in particular moderate-severe dementia; inability to perform most IADLs, especially managing medications; and most behavioral disturbances, especially agitation/aggression and appetite/eating problems. The article also suggests ways medical and mental health providers and researchers can help reduce caregiver stress.