Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource.

AIMS/HYPOTHESIS: Hyperglycaemia disproportionately affects African-Americans (AfAs). We tested the transferability of 18 single-nucleotide polymorphisms (SNPs) associated with glycaemic traits identified in European ancestry (EuA) populations in 5,984 non-diabetic AfAs. METHODS: We meta-analysed SNP associations with fasting glucose (FG) or insulin (FI) in AfAs from five cohorts in the Candidate Gene Association Resource. We: (1) calculated allele frequency differences, variations in linkage disequilibrium (LD), fixation indices (F(st)s) and integrated haplotype scores (iHSs); (2) tested EuA SNPs in AfAs; and (3) interrogated within ± 250 kb around each EuA SNP in AfAs. RESULTS: Allele frequency differences ranged from 0.6% to 54%. F(st) exceeded 0.15 at 6/16 loci, indicating modest population differentiation. All iHSs were <2, suggesting no recent positive selection. For 18 SNPs, all directions of effect were the same and 95% CIs of association overlapped when comparing EuA with AfA. For 17 of 18 loci, at least one SNP was nominally associated with FG in AfAs. Four loci were significantly associated with FG (GCK, p = 5.8 × 10(-8); MTNR1B, p = 8.5 × 10(-9); and FADS1, p = 2.2 × 10(-4)) or FI (GCKR, p = 5.9 × 10(-4)). At GCK and MTNR1B the EuA and AfA SNPs represented the same signal, while at FADS1, and GCKR, the EuA and best AfA SNPs were weakly correlated (r(2) <0.2), suggesting allelic heterogeneity for association with FG at these loci. CONCLUSIONS/INTERPRETATION: Few glycaemic SNPs showed strict evidence of transferability from EuA to AfAs. Four loci were significantly associated in both AfAs and those with EuA after accounting for varying LD across ancestral groups, with new signals emerging to aid fine-mapping.

Umbilical cord blood gas assessment of twins.

Umbilical cord arterial and venous blood gas values were compared in 63 twin pairs, of which 57 pairs had birth weights of 1500 g or more each. Small differences between the first and second twins existed for PO2, PCO2, and pH. However, bicarbonate values did not differ significantly. These cord gas differences represent minor respiratory aberrations, as reflected by a tendency toward carbon dioxide retention by the second twin. Route of delivery, time interval between deliveries, and nonvertex presentations were not associated with significant deviations from these observed acid-base patterns.

Excessive Daytime Sleepiness among Hypertensive US-Born Blacks and Foreign-Born Blacks: Analysis of the CAATCH Data.

Background. Evidence shows that blacks exhibit greater daytime sleepiness compared with whites, based on the Epworth Sleepiness Scale. In addition, sleep complaints might differ based on individuals' country of origin. However, it is not clear whether individuals' country of origin has any influence on excessive daytime sleepiness (EDS). Study Objectives. We tested the hypothesis that US-born blacks would show a greater level of EDS compared with foreign-born blacks. The potential effects of sociodemographic and medical risk were also determined. Design. We used the Counseling African-Americans to Control Hypertension (CAATCH) data. CAATCH is a group randomized clinical trial that was conducted among 30 community healthcare centers in New York, yielding baseline data for 1,058 hypertensive black patients. Results. Results of univariate logistic regression analysis indicated that US-born blacks were nearly twice as likely as their foreign-born black counterparts to exhibit EDS (OR = 1.87, 95% CI: 1.30-2.68, P < 0.001). After adjusting for effects of age, sex, education, employment, body mass index, alcohol consumption, and smoking habit, US-born blacks were 69% more likely than their counterparts to exhibit EDS (OR = 1.69, 95% CI: 1.11-2.57, P < 0.01). Conclusion. Findings demonstrate the importance of considering individuals' country of origin, in addition to their race and ethnicity, when analyzing epidemiologic sleep data.

Tibial dimensions before and during the recovery phase in the osteopetrotic mutant mouse.

Osteopetrosis is a genetic bone disease characterized by excessive bone mass and 'clubbing' of long bones. In the osteopetrotic (op) mouse, remission of the disease begins at 45 days of age. This study attempted to describe changes in the op tibia before and during remission. Osteopetrotic and normal littermates were killed at intervals from 10 to 120 days of age. Left tibiae were processed for transmission electron microscopy. Microradiographs of right tibiae were projected and drawn. Bone dimensions were compared between mutants and controls by ANOVA and bones were viewed in a scanning electron microscope. Differences between mutants and controls were: at all ages mutant tibiae were shorter than those of controls; 10-day distal shafts of mutant tibiae were significantly narrower; 30-day proximal shafts of mutant tibiae were wider, distal shafts were narrower, and there was no bone resorption along the external proximal metaphysis. At 48 days, resorption was seen along the proximal metaphyses of the mutant tibiae and by 60 days, extensive resorption areas were evident. However, proximal shafts of mutant tibiae were still significantly wider than those of controls. These results indicated that before remission there was an unequal deposition of bone on the mutant tibia. After remission, resorption occurred along the external proximal shaft, but was not enough to remove significant amounts of bone from the proximal metaphyses of mutant tibiae by 120 days of age.