Use of susceptibility scoring in conjunction with the genotypic transmission disequilibrium test

We explored the utility of selecting a genetically predisposed subgroup to increase the finding of a genetic signal in the Genetic Analysis Workshop 14 Collaborative Study on the Genetics of Alcoholism dataset. A subgroup of affected probands with low environmental risk exposures was defined using a susceptibility score calculated from an environmental risk model. Thirty-nine probands with highly positive scores were selected, along with their parents, for use in a genotypic transmission disequilibrium test (TDT) test. We compared the results of the genotypic TDT in this subgroup to the TDT results using all probands and their parents. For some markers, the susceptibility scoring approach resulted in smaller p-values, while for other markers, evidence for a genetic signal weakened. Further explorations into genetic and environmental population characteristics that benefit from this approach are warranted

P2‐540: Polygenetic Risk For Alzheimer’S Disease And Dementia Status

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153242/1/alzjjalz2019062948.pd

A simheuristic approach for evolving agent behaviour in the exploration for novel combat tactics

The automatic generation of behavioural models for intelligent agents in military simulation and experimentation remains a challenge. Genetic Algorithms are a global optimization approach which is suitable for addressing complex problems where locating the global optimum is a difficult task. Unlike traditional optimisation techniques such as hill-climbing or derivatives-based methods, Genetic Algorithms are robust for addressing highly multi-modal and discontinuous search landscapes. In this paper, we outline a simheuristic GA-based approach for automatic generation of finite state machine based behavioural models of intelligent agents, where the aim is the identification of novel combat tactics. Rather than evolving states, the proposed approach evolves a sequence of transitions. We also discuss workable starting points for the use of Genetic Algorithms for such scenarios, shedding some light on the associated design and implementation difficulties

P3‐558: Exposures Prior To Age 16 Are Associated With Dementia Status In The Health And Retirement Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152762/1/alzjjalz2019063595.pd

Traumatic Stress Interacts With Bipolar Disorder Genetic Risk to Increase Risk for Suicide Attempts

Objective Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). Method Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. Results After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041). Conclusion BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability

Neuropsychological Sequelae of Carotid Angioplasty with Stent Placement: Correlation with Ischemic Lesions in Diffusion Weighted Imaging

BACKGROUND AND PURPOSE: Few studies investigated the neuropsychological outcome after carotid angioplasty with stent placement (CAS), yielding partially inconsistent results. The present investigation evaluated the effect of CAS in patients with high-grade stenosis and assessed the predictive value of ischemic lesion number for postinterventional cognitive deterioration. METHODS: 22 patients were tested neuropsychologically before and six weeks after CAS. Cerebral ischemic changes were assessed with diffusion weighted imaging (DWI) prior to and after angioplasty. RESULTS: Pre- to postinterventional cognitive performance improved significantly in terms of verbal memory (t = -2.30; p<0.05), whereas significant deterioration was noted regarding verbal memory span (t = 2.31; p<0.05). 8 (36%) persons conformed to the criteria of cognitive improvement. 6 patients (27%) were postinterventionally classified as having deficits. Analysis yielded no statistically significant correlations between lesion quantity and cognitive change. CONCLUSION: Both improvement and deterioration of cognitive functioning was observed in our collective of patients, leaving the neuropsychological outcome after percutaneous transluminal angioplasty unpredictable in individual cases. The presence of acute ischemic lesions on DWI was found to be not tightly associated with cognitive dysfunction after CAS

Wastewater irrigation: the state of play

As demand for fresh water intensifies, wastewater is frequently being seen as a valuable resource. Furthermore, wise reuse of wastewater alleviates concerns attendant with its discharge to the environment. Globally, around 20 million ha of land are irrigated with wastewater, and this is likely to increase markedly during the next few decades as water stress intensifies. In 1995, around 2.3 billion people lived in water-stressed river basins and this could increase to 3.5 billion by 2025. We review the current status of wastewater irrigation by providing an overview of the extent of the practice throughout the world and through synthesizing the current understanding of factors influencing sustainable wastewater irrigation. A theme that emerges is that wastewater irrigation is not only more common in water-stressed regions such as the Near East, but the rationale for the practice also tends to differ between the developing and developed worlds. In developing nations, the prime drivers are livelihood dependence and food security, whereas environmental agendas appear to hold greater sway in the developed world. The following were identified as areas requiring greater understanding for the long-term sustainability of wastewater irrigation: (i) accumulation of bioavailable forms of heavy metals in soils, (ii) environmental fate of organics in wastewater-irrigated soils, (iii) influence of reuse schemes on catchment hydrology, including transport of salt loads, (iv) risk models for helminth infections (pertinent to developing nations), (v) microbiological contamination risks for aquifers and surface waters, (vi) transfer efficiencies of chemical contaminants from soil to plants, (vii) health effects of chronic exposure to chemical contaminants, and (viii) strategies for engaging the public.<br /

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genome-wide Association Study of Change in Fasting Glucose over time in 13,807 non-diabetic European Ancestry Individuals

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 x 10(-8)) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.Peer reviewe