Kate 2012

Each year, kate seeks to: explore ideas about normative gender, sex, and sexuality work against oppression and hierarchies of power in any and all forms serve as a voice for race and gender equity as well as queer positivity encourage the silent to speak and feel less afraid build a zine and community that we care about and trusthttps://digitalcommons.otterbein.edu/kate/1007/thumbnail.jp

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Novel \u3cem\u3eEhrlichia\u3c/em\u3e sp. Pathogenic for Humans in the Midwestern United States: Human Cases 2009 - 2011 and Results of Tick, Rodent, and Deer Studies

We recently reported a novel Ehrlichia sp. closely related to E. muris detected in blood of 4 from patients in Minnesota (MN) and Wisconsin (WI) in 2009 (NEJM 2011). We now present data from the 2009-2011 patient cases, and results of tick, rodent, and deer studies. Blood from patients with suspected ehrlichiosis or anaplasmosis was tested using PCR targeting the Ehrlichia/Anaplasma Heat Shock Operon gene. PCR was also performed on rodent and deer blood, ticks from MN and WI, and ticks found on military personnel at 132 U.S. military bases nationwide (2007-2010). Select specimens were characterized using culture and DNA sequencing. Human sera were tested for antibodies to specific Ehrlichia spp. and A. phagocytophilum. During 6/2009-8/2011, blood from 32 of 8,110 MN and WI patients tested PCR positive for an Ehrlichia sp. other than E. chaffeensis and E. ewingii. This result was also detected from 1 North Dakota patient who recently travelled to MN. The result was not noted among 7,827 other patient specimens from other states. An Ehrlichia sp. was also cultured from the blood of one WI patient. The 16S rRNA gene (rrs) sequence of clinical and culture isolates was most similar to E. muris (98%). Patients comprised 22 men and 11 women, aged 23 - 87 years. Among patients with available data, infection manifested with fever (31/33), headache (26/33) lymphopenia (7/12) and thrombocytopenia (14/19); 4 of 33 were hospitalized (≤3 days) and 32 of 33 recovered following doxycycline treatment. One patient recovered without treatment. Three of 3 patients had a higher antibody titer to the novel Ehrlichia sp. than E. chaffeensis. No antibodies to A. phagocytophilum antigens were detected. Thirty-four of 1,384 I. scapularis ticks from MN and WI were PCR positive for the novel Ehrlichia, whereas it was not detected in I. scapularis from other states (n=2931) or other tick species (n=6563). Two of 147 rodents and 0 of 180 deer tested were PCR positive. Based on these data, the novel Ehrlichia sp. appears to circulate in a region where Ehrlichiae have not historically been considered endemic and causes a disease which is clinically and epidemiologically similar to human monocytic ehrlichiosis due to E. chaffeensis. These findings should be taken into consideration for diagnosis and surveillance

Colour variation in cichlid fish:Developmental mechanisms, selective pressures and evolutionary consequences

<p>Cichlid fishes constitute one of the most species-rich families of vertebrates. In addition to complex social behaviour and morphological versatility, they are characterised by extensive diversity in colouration, both within and between species. Here, we review the cellular and molecular mechanisms underlying colour variation in this group and the selective pressures responsible for the observed variation. We specifically address the evidence for the hypothesis that divergence in colouration is associated with the evolution of reproductive isolation between lineages. While we conclude that cichlid colours are excellent models for understanding the role of animal communication in species divergence, we also identify taxonomic and methodological biases in the current research effort. We suggest that the integration of genomic approaches with ecological and behavioural studies, across the entire cichlid family and beyond it, will contribute to the utility of the cichlid model system for understanding the evolution of biological diversity. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.</p>

Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

OBJECTIVES: Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients. METHODS: A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models. RESULTS: BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment. CONCLUSIONS: The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype

Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li-PGS(+)) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li-PGS(+) was developed in the International Consortium of Lithium Genetics cohort (ConLi(+)Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li-PGS(+) and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P &lt; 0.05. Li-PGS(+) was positively associated with lithium treatment response in the ConLi(+)Gen cohort, in both the categorical (P = 9.8 x 10(-)(12), R-2 = 1.9%) and continuous (P = 6.4 x 10(-)(9), R-2 = 2.6%) outcomes. Compared to bipolar patients in the 1(st) decile of the risk distribution, individuals in the 10(th) decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 x 10(-)(4), R-2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li-PGS(+) may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment