Susceptibility gene identification and risk evaluation model construction by transcriptome-wide association analysis for salt sensitivity of blood pressure.

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. METHODS AND RESULTS: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets. CONCLUSIONS: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals.

[Health Utility of Patients with Stroke Measured by EQ-5D and SF-6D].

OBJECTIVE: To compare EQ-5D and SF-6D for measuring health utility of stroke patients in health economic evaluation studies. METHODS: A prospective cohort study was conducted on 596 stroke patients in the West China Hospital of Sichuan University from 2010 to 2016. Data were collected at baseline through face to face interviews and at the follow-up stages through telephone interviews with a three-month interval. EQ-5D and SF-6D were used for measuring health utility scores of the participants. The consistency of the two instruments was assessed using Bland-Altman plot and Intraclass correlation coefficient (ICC) . Logistic regression models were established to identify predictors of health utility. RESULTS: The participants had a mean utility score of 0.78 (95% confidence interval:0.76, 0.80) in EQ-5D,compared with 0.74 (95% confidence interval: 0.73, 0.76) in SF-6D,and a median (interquartile range) of 0.86 (0.68, 1.00) in EQ-5D and 0.73 (0.62, 0.86) in SF-6D. The 95% limits of agreement between the two instruments ranged from -0.28 to 0.35,with an ICC of 0.67 (95% confidence interval: 0.62,0.71). EQ-5D had a higher ceiling effect. The health utility score of stroke patients changed there rapidly in acute phase (less than 3 months) but barely changed there after.Severity of stroke was a major predictor of health utility scores. CONCLUSION: The two instruments generate inconsistent results in health utility. SF-6D is better for measuring health utility in patients with stroke in China.

Factors associated with mortality and length of stay in hospitalised neonates in Eritrea, Africa: a cross-sectional study.

OBJECTIVE: To determine the factors associated with mortality in a hospitalised cohort of infants in Asmara, Eritrea. DESIGN: Retrospective cross-sectional review of all 2006 admissions to a specialised neonatal intensive care unit. Data on gestational age (prematurity), age at presentation, birth weight, gender, mode of delivery, Apgar score, maternal age, birth location, admission diagnosis, admission comorbidities, time of admission and outcome were collected. SETTING: Orotta Pediatric Hospital 'Specialised Neonatal Intensive Care Unit' (SNCU) in Orotta National Maternity Referral Hospital, the nation's only tertiary newborn centre. PRIMARY AND SECONDARY OUTCOME MEASURES: Factors associated with mortality and length of stay via multivariate regression analysis and the combined association of both hypothermia and pneumonia. Other outcome measures were determination of the association of admission hypothermia, time of admission and pneumonia on mortality. RESULTS: A total of 1502 infants were admitted to the SNCU with an average preterm gestational age of 35.9 weeks. 87 died (mortality 8.2%). In bivariate analysis, the highest mortality rate (10.3%) was seen in patient's admitted <1 h after birth. Patients with hypothermia or pneumonia exhibited higher mortality rates (13.6% and 13.4%, respectively). In multivariate analysis, birth weight <2 kg (p<0.01), birth weight between 2.1 and 2.5 kg (p<0.01), Apgar score at 1 min (p<0.01), small for gestational age (p<0.01), hypothermia (p<0.04) and pneumonia (p<0.01) were associated with mortality. CONCLUSION: Hypothermia, pneumonia, younger gestational age, 1 min Apgar score and small size for gestational age are significantly associated with mortality and longer length of stay in the Eritrean SNCU.

Influenza vaccination rates of expectant parents with neonatal intensive care admission.

OBJECTIVES: To ascertain the rate of influenza immunization in pregnant couples whose infants required neonatal intensive care unit (NICU) admission, and to clarify predictors for trivalent inactivated influenza vaccine (TIV) use in this targeted parent population. STUDY DESIGN: During the 2005-07 influenza seasons, parents of NICU patients at two level III centers were surveyed about TIV after their infant's NICU admission. Data on immunization history, location of immunization, and other risk factors for influenza were assessed. Infant data including birth weight, gestational age, and multiple births were also obtained. RESULTS: Seven hundred and eighty-six parents had infants in the NICU. Five hundred and forty-seven (69.5%) were surveyed. The overall parental rate of vaccination was 23.2% (127/547). The parental vaccination rate did not differ between years (23.2% vs. 23.2%). Mothers were less likely to have received TIV prior to delivery than fathers (17.0% vs. 28.4%; p < 0.02). Of the population, 19.3% received immunization from their OB/GYN. A concordance rate of 8.9% was noted between married couples receiving TIV. More parents received TIV in January and February of the influenza seasons than November and December (p < 0.05, Student's t-test). Influenza immunization rate in NICU parents was unrelated to infant's gestational age, parental age, total number of risk factors for TIV, hospital length of stay, multiple gestation, or need for high risk obstetrical care. CONCLUSIONS: TIV rates among high-risk pregnant parents whose infants are admitted to NICU are lower than expected compared with the general population. Patient refusal of influenza vaccine is not a major obstacle toward acceptance.