Asymptotically minimax Bayes predictive densities

Given a random sample from a distribution with density function that depends on an unknown parameter $\theta$, we are interested in accurately estimating the true parametric density function at a future observation from the same distribution. The asymptotic risk of Bayes predictive density estimates with Kullback--Leibler loss function $D(f_{\theta}||{\hat{f}})=\int{f_{\theta} \log{(f_{\theta}/ hat{f})}}$ is used to examine various ways of choosing prior distributions; the principal type of choice studied is minimax. We seek asymptotically least favorable predictive densities for which the corresponding asymptotic risk is minimax. A result resembling Stein's paradox for estimating normal means by the maximum likelihood holds for the uniform prior in the multivariate location family case: when the dimensionality of the model is at least three, the Jeffreys prior is minimax, though inadmissible. The Jeffreys prior is both admissible and minimax for one- and two-dimensional location problems.Comment: Published at http://dx.doi.org/10.1214/009053606000000885 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Long-term negative emotional outcomes of warzone TBI

Objective: Many veterans of the Iraq and Afghanistan Wars have experienced traumatic brain injury (TBI). Although prior work has examined associations between TBI and development of psychi- atric syndromes, less is known about associations between TBI and component emotions constituting these syndromes, especially in the long term. The purpose of this study was to examine the long-term emotional consequences of deployment-related TBI. Methods: As part of VA Cooperative Studies Program #566, we assessed a sample of n1⁄4456US Army soldiers prior to an index deployment to Iraq, and again an average of 8.3 years (SD1⁄42.4years) after their deployment for a long-term follow-up assessment. In this report, we used adjusted regression analyses to examine the relationship of deployment TBI to depression, anxiety, and stress symptom severity measured at the long-term follow-up assessment. A structured interview was used to determine TBI history; the Depression, Anxiety, and Stress Scale, 21-item version (DASS-21) was used to determine emotional status at the follow-up evaluation. Results: Warzone TBI events, particularly when greater than mild in severity, were independently associated with depression, anx- iety, and stress severity at long-term follow-up, even after taking into account variance attributable to pre-deployment emotional distress and war-zone stress. Post-hoc analyses did not detect independent associations of either number of events or injury mechanism with outcomes. Conclusions: These findings highlight the potentially enduring and multi-faceted emotional effects of deployment TBI, underscor- ing the need for early assessment of negative affectivity in war- zone veterans reporting TBI

Long-term negative emotional outcomes of warzone TBI

Objective: Many veterans of the Iraq and Afghanistan Wars have experienced traumatic brain injury (TBI). Although prior work has examined associations between TBI and development of psychi- atric syndromes, less is known about associations between TBI and component emotions constituting these syndromes, especially in the long term. The purpose of this study was to examine the long-term emotional consequences of deployment-related TBI. Methods: As part of VA Cooperative Studies Program #566, we assessed a sample of n1⁄4456US Army soldiers prior to an index deployment to Iraq, and again an average of 8.3 years (SD1⁄42.4years) after their deployment for a long-term follow-up assessment. In this report, we used adjusted regression analyses to examine the relationship of deployment TBI to depression, anxiety, and stress symptom severity measured at the long-term follow-up assessment. A structured interview was used to determine TBI history; the Depression, Anxiety, and Stress Scale, 21-item version (DASS-21) was used to determine emotional status at the follow-up evaluation. Results: Warzone TBI events, particularly when greater than mild in severity, were independently associated with depression, anx- iety, and stress severity at long-term follow-up, even after taking into account variance attributable to pre-deployment emotional distress and war-zone stress. Post-hoc analyses did not detect independent associations of either number of events or injury mechanism with outcomes. Conclusions: These findings highlight the potentially enduring and multi-faceted emotional effects of deployment TBI, underscor- ing the need for early assessment of negative affectivity in war- zone veterans reporting TBI

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

S93. GENOMICS OF SUICIDAL IDEATION AND BEHAVIOR IN VETERANS WITH SCHIZOPHRENIA AND BIPOLAR ILLNESS

Abstract Background Suicide is a major problem in severe mental illness (SMI), with increased risk for lifetime suicidal ideation and behavior compounded in veterans. Previous research has suggested that genomic risk factors exist for suicidal ideation and behavior, and we examined the genomic correlates of suicidal ideation and behavior in 8,049 male and 1,290 female veterans with schizophrenia or bipolar disorder. Methods Data were collected previously on demographic, clinical, and functional status factors, as well as self-reported suicidal ideation and behavior assessed with the Columbia Suicide Severity Rating Scale (lifetime version). For this study, we defined an ideation and behavior as a single latent trait, excluding patients with non-suicidal self-injurious behavior. A customized Affymetrix Axiom Biobank array was used to obtain genotype data. After sample and variant quality control steps and ancestry inference, analyses included 657,459 SNPs and 4,012 European American samples (with 3,223 cases and 789 controls, which include 3,507 males and 505 females), as well as 2,651 African American samples (with 1,955 cases and 696 controls, which include 2,249 males and 402 females). The results were then filtered with the imputation quality score R2>0.8, MAF>0.01, and Hardy-Weinberg equilibrium test p-value >1 x 10–6; a GWAS p-value threshold of 5 x 10–8 was adopted as genome-wide statistical significance. We performed both SNP-based analysis and gene-based analysis (using the UTMOST approach that leverages eQTL information across tissues from the GTEx project). To investigate the genetic correlation between the ideation and behavior score in the combined sample and other complex traits, we applied GNOVA, a framework to estimate the genetic overlap of ideation and behavior scores in schizophrenia or bipolar samples with respect to 2,626 traits from the UK Biobank (UKB) and other GWAS results. FDR was used to correct for multiple testing, and a q value<0.05 was set as the threshold for statistical significance. Results For European American (EA) and African American (AA) ancestry patients, no SNP passed the 5 x 10–8 the genome wide statistical significance; 4 SNPs were significant at 10–6 for the EA group, and 8 SNPs for the AA group. Gene-level analysis (UTMOST) identified 5 genes (GAMT 1.74×10–11, FTL 1.84×10–11, DCTN4 2.97×10–9, IYVE1 4.38×10–9, IQCC 7.07×10–9) from the EA group with suicide tendency; several had previously-noted clinical significance. For the GNOVA results, 25 traits showed statistically significant correlation at 10–3, and three survived FDR correction: depression in the past 2 weeks, miserableness, and tenseness in the past 2 weeks. All of the 25 traits described a mood or physical condition, but none of the traits included schizophrenia or bipolar disorder. Discussion Genomic correlates of suicidal ideation and behavior relate to traits in the general population that are linked to physical illness, mood, or anxiety. These findings suggest a commonality of genomic risk factors for suicidal ideation and behavior across SMI and the general population

‘Race’ and Prostate Cancer Mortality in Equal-access Healthcare Systems

BackgroundReports suggest worse health-related outcomes among black (vs white) men diagnosed with prostate cancer, but appropriate cause-effect inferences are complicated by the relationship of race and other prognostic factors.MethodsWe searched the literature to find contemporary articles focusing on mortality among black and white men with prostate cancer in equal-access healthcare systems. We also directly assessed the association of race and prostate cancer mortality by conducting an observational cohort analysis of 1270 veterans diagnosed with prostate cancer and followed for 11 to 16 years at 9 medical centers within the Veterans Health Administration.ResultsAmong 5 reports providing quantitative results for the association of race and mortality among men with prostate cancer in equal-access systems, outcomes were similar for black and white men. Race also was not a prognostic factor in the observational cohort analysis of US veterans, with an adjusted hazard ratio for black (vs white) men and prostate cancer mortality of 0.90 (95% confidence interval, 0.58-1.40; P = .65).ConclusionsMortality among black and white patients with prostate cancer is similar in equal-access healthcare systems. Studies that find racial differences in mortality (including cause-specific mortality) among men with prostate cancer may not account fully for socioeconomic and clinical factors