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

Patterns of Healthcare Use and Mortality After Alzheimer's Disease or Related Dementia Diagnosis Among Alaska Native Patients: Results of a Cluster Analysis in a Tribal Healthcare Setting

Background: Alaska Native and American Indian (AN/AI) people represent a rapidly aging population with disproportionate burdens of Alzheimer's disease and related dementias (ADRD) risk factors. Objective: To characterize healthcare service use patterns and mortality in the years following ADRD diagnosis for patients in an Alaska Native Tribal health system. Methods: The study sample included all AN/AI patients aged 55 or older with an ADRD diagnosis who were seen between 2012-2018 (n = 407). We used cluster analysis to identify distinct patterns of healthcare use for primary care, emergency and urgent care, inpatient hospital stays, and selected specialty care. We compared demographic and clinical factors between clusters and used regression to compare mortality. Results: We identified five clusters of healthcare service use patterns after ADRD diagnosis: 1) people who use a low amount of all services (n = 107), 2) people who use a high amount of all services (n = 60), 3) people who use a high amount of primary and specialty care (n = 105), 4) people who use a high amount of specialty care (n = 65), and 5) people who use a high amount of emergency and urgent care (n = 70). The cluster with the highest use had the greatest proportion of comorbidities and had a 2.3-fold increased risk of mortality compared to the cluster with the lowest healthcare service use. Conclusion: Results indicate that those receiving the most services had the greatest healthcare-related needs and increased mortality. Future research could isolate factors that predict service use following ADRD diagnosis and identify other differential health risks

Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease : A prospective study in eight cohorts

Introduction: Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. Methods: We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four cohorts were used for discovery with replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented. Results: Over 246,698 person-years, 995 and 745 cases of incident dementia and Alzheimer's disease were detected, respectively. Three branched-chain amino acids (isoleucine, leucine, and valine), creatinine and two very low density lipoprotein (VLDL)-specific lipoprotein lipid subclasses were associated with lower dementia risk. One high density lipoprotein (HDL; the concentration of cholesterol esters relative to total lipids in large HDL) and one VLDL (total cholesterol to total lipids ratio in very large VLDL) lipoprotein lipid subclass was associated with increased dementia risk. Branched-chain amino acids were also associated with decreased Alzheimer's disease risk and the concentration of cholesterol esters relative to total lipids in large HDL with increased Alzheimer's disease risk. Discussion: Further studies can clarify whether these molecules play a causal role in dementia pathogenesis or are merely markers of early pathology. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.Peer reviewe

Systematic study of nuclear effects in pp ++Al, pp ++Au, dd ++Au, and 3^{3}He++Au collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV using π0\pi^0 production

International audienceThe PHENIX collaboration presents a systematic study of $\pi^0$ production from $p$ $+$ $p$, $p$ $+$Al, $p$ $+$Au, $d$ $+$Au, and $^{3}$He$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV. Measurements were performed with different centrality selections as well as the total inelastic, 0%--100%, selection for all collision systems. For 0%--100% collisions, the nuclear modification factors, $R_{xA}$, are consistent with unity for $p_T$ above 8 GeV/$c$, but exhibit an enhancement in peripheral collisions and a suppression in central collisions. The enhancement and suppression characteristics are similar for all systems for the same centrality class. It is shown that for high-$p_T$-$\pi^0$ production, the nucleons in the $d$ and $^3$He interact mostly independently with the Au nucleus and that the counter intuitive centrality dependence is likely due to a physical correlation between multiplicity and the presence of a hard scattering process. These observations disfavor models where parton energy loss has a significant contribution to nuclear modifications in small systems. Nuclear modifications at lower $p_T$ resemble the Cronin effect -- an increase followed by a peak in central or inelastic collisions and a plateau in peripheral collisions. The peak height has a characteristic ordering by system size as $p$ $+$Au $>$ $d$ $+$Au $>$ $^{3}$He$+$Au $>$ $p$ $+$Al. For collisions with Au ions, current calculations based on initial state cold nuclear matter effects result in the opposite order, suggesting the presence of other contributions to nuclear modifications, in particular at lower $p_T$

Systematic study of nuclear effects in pp ++Al, pp ++Au, dd ++Au, and 3^{3}He++Au collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV using π0\pi^0 production

International audienceThe PHENIX Collaboration presents a systematic study of inclusive π0 production from p+p, p+Al, p+Au, d+Au, and He3+Au collisions at sNN=200GeV. Measurements were performed with different centrality selections as well as the total inelastic, 0–100%, selection for all collision systems. For 0–100% collisions, the nuclear-modification factors, RxA, are consistent with unity for pT above 8GeV/c, but exhibit an enhancement in peripheral collisions and a suppression in central collisions. The enhancement and suppression characteristics are similar for all systems for the same centrality class. It is shown that for high-pT-π0 production, the nucleons in the d and He3 interact mostly independently with the Au nucleus and that the counterintuitive centrality dependence is likely due to a physical correlation between multiplicity and the presence of a hard scattering process. These observations disfavor models where parton energy loss has a significant contribution to nuclear modifications in small systems. Nuclear modifications at lower pT resemble the Cronin effect—an increase followed by a peak in central or inelastic collisions and a plateau in peripheral collisions. The peak height has a characteristic ordering by system size as p+Au>d+Au>He3+Au>p+Al. For collisions with Au ions, current calculations based on initial-state cold nuclear matter effects result in the opposite order, suggesting the presence of other contributions to nuclear modifications, in particular at lower pT

Transverse-single-spin asymmetries of charged pions at midrapidity in transversely polarized p+pp{+}p collisions at s=200\sqrt{s}=200 GeV

International audienceIn 2015, the PHENIX Collaboration has measured single-spin asymmetries for charged pions in transversely polarized p+p collisions at the center-of-mass energy of s=200  GeV. The pions were detected at central rapidities of |η|<0.35. The single-spin asymmetries are consistent with zero for each charge individually, as well as consistent with the previously published neutral-pion asymmetries in the same rapidity range. However, they show a slight indication of charge-dependent differences which may suggest a flavor dependence in the underlying mechanisms that create these asymmetries