Genome-wide association for major depression through age at onset stratification:Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Background Major depressive disorder (MDD) is a disabling mood disorder and, despite a known heritable component, a large meta-analysis of GWAS revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age-at-onset (AAO) in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by AAO. Method Discovery case-control GWASs were performed where cases were stratified using increasing/decreasing AAO-cutoffs; significant SNPs were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 controls for sub-setting. Polygenic score analysis was used to examine if differences in shared genetic risk exists between earlier and adult onset MDD with commonly co-morbid disorders of schizophrenia, bipolar disorder, Alzheimer’s disease, and coronary artery disease. Results We identify one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, OR=1.16, 95%CI=1.11-1.21, p=5.2x10-11). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset. Conclusions We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder

Navigation, mixed reality, and robotics in endoscopic spine surgery

Endoscopic spine surgery (ESS) is an ultra-minimally invasive technique through which spinal pathology can be addressed via sub-centimeter incisions with negligible soft tissue disruption. However, concerns exist regarding the steep learning curve, operative time, and radiation exposure to the surgical team. The use of intraoperative navigation, mixed reality, and robotics in the setting of ESS is currently being explored, and the early evidence suggests that such technologies may help mitigate these issues. The application of these technologies in ESS as well as the associated literature is reviewed herein

The Risk for Infant Mortality among Adolescent Childbearing Groups

Objective: To evaluate risk disparities and risk factors for infant mortality among adolescent childbearing age groups. Methods: We combined the 1995 and 1996 comprehensive U.S. birth cohorts provided by the National Center for Heath Statistics. Our analysis included 777,762 singleton, first births to women aged 12-19 years linked to 4631 infant deaths. We used both bivariate comparisons and multivariable logistic regression for our analysis, with infant mortality as our main outcome measure. Results: Rates of infant mortality are substantially higher for ≤15-year-olds (8.1/1000 live births) compared with 16-17-year-olds (6.3/1000 live births) and 18-19-year-olds (5.4/1000 live births). Even after adjusting for risk factors associated with poor outcomes, including alcohol use, tobacco use, and prenatal care use, the risk for infant mortality was 1.6 (95% confidence interval [95% CI] 1.4, 1.7) times greater for infants of mothers ≤15 years old as compared with those mothers 18-19 years old. In the ≤15-year-old group, 62% of fathers were not reported on the child's birth certificate. Not reporting the father was associated with a 24% increased risk for infant mortality after adjusting for maternal and infant risk factors. Conclusions: Childbearing in ≤15-year-olds is associated with a substantial increased risk for infant mortality compared with childbearing in older adolescence. This study suggests that not reporting the father on a birth certificate is a potential risk marker. Risk differences among adolescent age groups may be important to consider when creating tailored intervention and prevention strategies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63403/1/154099902762203722.pd