Genetic association study of Preterm birth and Gestational age in a population-based case-control study in Peru: Genetics of PTB and GA in pregnant women in Peru.

Preterm birth (PTB) is an adverse pregnancy outcome affecting ~15 million pregnancies worldwide. Genetic studies have identified several candidate loci for PTB, but results remain inconclusive and limited to European populations. Thus, we conducted a genome-wide association study (GWAS) of PTB and gestational age at delivery (GA) among 2,212 Peruvian women. PTB cases delivered ≥ 20 weeks' but < 37 weeks' gestation, while controls delivered at term (≥ 37 weeks but < 42 weeks). After imputation (TOPMED) and quality control, we assessed the association of ~6 million SNPs with PTB and GA using multivariable regression models adjusted for maternal age and the first two genetic principal components. In silico functional analysis (FUMA-GWAS) was conducted among top signals detected with an arbitrary P < 1.0×10-5 in each GWAS. We sought to replicate genetic associations with PTB and GA identified in Europeans, and we developed a genetic risk score for GA based on European markers. Mean GA was 30 ± 4 weeks in PTB cases (N=933) and 39 ± 1 in the controls (N=1,279). PTB cases were slightly older and had higher C-sections and vaginal bleeding than controls. No association was identified at genome-wide level. Top suggestive (P < 1.0×10-5) signals were seen at rs13151645 (LINC01182) for PTB, and at rs72824565 (CTNNA2) for GA. Top PTB variants were enriched for biological pathways associated with polyketide, progesterone, steroid hormones, and glycosyl metabolism. Top GA variants were enriched in intronic regions and cancer pathways, and these genes were upregulated in the brain and subcutaneous adipose tissue. In combination with non-genetic risk factors, top SNPs explained 14% and 15% of the phenotypic variance of PTB and GA in our sample, but these results need to be interpreted with caution. Variants in WNT4 associated with GA in Europeans were replicated in our study. The genetic risk score based in European markers, was associated with a 2-day longer GA (R2=0.003, P=0.002) per standard deviation increase in the score in our sample. This genetic association study identified various signals suggestively associated with PTB and GA in a non-European population; they were linked to relevant biological pathways related to the metabolism of progesterone, prostanoid, and steroid hormones, and genes associated with GA were significantly upregulated in relevant tissues for the pathophysiology of PTB based on the in-silico functional analysis. None of these top variants overlapped with signals previously identified for PTB or GA in Europeans.

Personal and Work-Related Burnout Is Associated with Elevated Diastolic Blood Pressure and Diastolic Hypertension among Working Adults in Chile.

We aimed at investigating the association of personal and work-related burnout with blood pressure and hypertension among working adults in Chile. We conducted a cross-sectional study among 1872 working adults attending the Hospital del Trabajador in Santiago, Chile, between September 2015 and February 2018. The Copenhagen Burnout Inventory was used to assess personal and work-related burnout. Blood pressure was measured by medical practitioners. Multivariable linear and logistic regressions were used to estimate the association of burnout status with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension. After adjusting for confounders, participants with both types of burnout had a 1.66 (95% confidence interval [CI]: 0.02-3.30) mmHg higher mean DBP than those without burnout. The odds of isolated diastolic hypertension among the participants with only personal burnout and both types of burnout were 2.00-fold (odds ratio [OR] = 2.00; 95% CI: 1.21-3.31) and 2.08-fold (OR = 2.08; 95% CI: 1.15-3.78) higher than those without burnout. The odds of combined systolic/diastolic hypertension among the participants with only work-related burnout increased by 59% (OR = 1.59; 95% CI: 1.01-2.50) compared with those without burnout. Both work-related and personal burnouts were associated with increased DBP and odds of diastolic hypertension among working adults in Chile.

Pain, mood, and suicidal behavior among injured working adults in Chile.

BACKGROUND: Chronic pain is comorbid with psychiatric disorders, but information on the association of chronic pain with depressive symptoms, generalized anxiety, and suicidal behavior among occupational cohorts is inadequate. We investigated these associations among employed Chilean adults. METHODS: A total of 1946 working adults were interviewed during their outpatient visit. Pain was assessed using the Short Form McGill Pain questionnaire (SF-MPG) while depression and generalized anxiety were examined using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. The Columbia-Suicide Severity Rating Scale was used to assess suicidal behavior and suicidal ideation. Multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95%CI) for the association of chronic pain with mood disorders, as well as suicidal behavior. RESULTS: High chronic pain (SF-MPG > 11) was reported by 46% of participants. Approximately two-fifths of the study participants (38.2%) had depression, 23.8% generalized anxiety, 13.4% suicidal ideation, and 2.4% suicidal behavior. Compared to those with low pain (SF-MPG ≤11), participants with high chronic pain (SF-MPG > 11) had increased odds of experiencing depression only (aOR = 2.87; 95% CI: 2.21-3.73), generalized anxiety only (aOR = 2.38; 95% CI: 1.42-3.99), and comorbid depression and generalized anxiety (aOR = 6.91; 95% CI: 5.20-9.19). The corresponding aOR (95%CI) for suicidal ideation and suicidal behavior were (aOR = 2.20; 95% CI: 1.58-3.07) and (aOR = 2.18 = 95% CI: 0.99-4.79), respectively. CONCLUSIONS: Chronic pain is associated with increased odds of depression, generalized anxiety, and suicidal behavior. Mental health support and appropriate management of patients experiencing chronic pain are critical.

Evaluating the performance of the Pain Interference Index and the Short Form McGill Pain Questionnaire among Chilean injured working adults.

BACKGROUND: Chronic pain can lead to economic instability, decreased job productivity, and poor mental health. Therefore, reliable identification and quantification of chronic pain is important for clinical diagnosis and treatment. OBJECTIVE: To determine the psychometric properties of the Spanish language versions of the Pain Interference Index (PII) and the Short Form McGill Pain Questionnaire (SF-MPG) among a population of working adults who experienced injury in Santiago, Chile. METHODS: A total of 1,975 participants with work-related injuries were interviewed to collect sociodemographic, occupational, and chronic pain characteristics. Construct validity and factorial structure of the PII and SF-MPG were assessed through exploratory factor analyses (EFA). Cronbach's alpha was used to evaluate internal consistency. RESULTS: The PII mean score was 3.84 ± 1.43 among all participants. The SF-MPG median score was 11 [IQR: 6-16] in this study population. Cronbach's alpha for the PII was 0.90 and 0.87 for the SF-MP. EFA resulted in a one factor solution for the PII. A two-factor solution was found for the SF-MPG. The two-factors for SF-MPG were sensory and affective subscales with Cronbach's alpha of 0.82 and 0.714, respectively. When the two scales were combined, an EFA analysis confirmed the PII and SF-MPG measure different aspects of chronic pain. CONCLUSIONS: The PII and SF-MPG had good construct validity and reliability for assessing different aspects of chronic pain among working Chilean adults.