Browsing by Author "Jain, Sonia"

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    Association of Brain Injury Biomarkers and Circulatory Shock Following Moderate-Severe Traumatic Brain Injury: A TRACK-TBI Study.
    (Journal of neurosurgical anesthesiology, 2021-12) Toro, Camilo; Jain, Sonia; Sun, Shelly; Temkin, Nancy; Barber, Jason; Manley, Geoffrey; Komisarow, Jordan M; Ohnuma, Tetsu; Foreman, Brandon; Korley, Frederick; James, Michael L; Laskowitz, Daniel; Vavilala, Monica S; Hernandez, Adrian; Mathew, Joseph P; Markowitz, Amy J; Krishnamoorthy, Vijay; TRACK-TBI Investigators

    Introduction

    Early circulatory shock following traumatic brain injury (TBI) is a multifactorial process; however, the impact of brain injury biomarkers on the risk of shock has not been evaluated. We examined the association between neuronal injury biomarker levels and the development of circulatory shock following moderate-severe TBI.

    Methods

    In this retrospective cohort study, we examined adults with moderate-severe TBI (Glasgow Coma Scale score <13) enrolled in the TRACK-TBI study, an 18-center prospective TBI cohort study. The exposures were day-1 levels of neuronal injury biomarkers (glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1 [UCH-L1], S100 calcium-binding protein B [S100B], neuron-specific enolase), and of an inflammatory biomarker (high-sensitivity C-reactive protein). The primary outcome was the development of circulatory shock, defined as cardiovascular Sequential Organ Failure Assessment Score ≥2 within 72 hours of admission. Association between day-1 biomarker levels and the development of circulatory shock was assessed with regression analysis.

    Results

    The study included 392 subjects, with a mean age of 40 years; 314 (80%) were male and 165 (42%) developed circulatory shock. Median (interquartile range) day-1 levels of UCH-L1 (994.8 [518.7 to 1988.2] pg/mL vs. 548.1 [280.2 to 1151.9] pg/mL; P<0.0001) and S100B (0.47 μg/mL [0.25 to 0.88] vs. 0.27 [0.16 to 0.46] μg/mL; P<0.0001) were elevated in those who developed early circulatory shock compared with those who did not. In multivariable regression, there were associations between levels of both UCH-L1 (odds ratio, 1.63 [95% confidence interval, 1.25-2.12]; P<0.0005) and S100B (odds ratio, 1.73 [95% confidence interval 1.27-2.36]; P<0.0005) with the development of circulatory shock.

    Conclusion

    Neuronal injury biomarkers may provide the improved mechanistic understanding and possibly early identification of patients at risk for early circulatory shock following moderate-severe TBI.
  • Thumbnail Image
    ItemOpen Access
    GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
    (The American journal of psychiatry, 2023-10) Docherty, Anna R; Mullins, Niamh; Ashley-Koch, Allison E; Qin, Xuejun; Coleman, Jonathan RI; Shabalin, Andrey; Kang, JooEun; Murnyak, Balasz; Wendt, Frank; Adams, Mark; Campos, Adrian I; DiBlasi, Emily; Fullerton, Janice M; Kranzler, Henry R; Bakian, Amanda V; Monson, Eric T; Rentería, Miguel E; Walss-Bass, Consuelo; Andreassen, Ole A; Behera, Chittaranjan; Bulik, Cynthia M; Edenberg, Howard J; Kessler, Ronald C; Mann, J John; Nurnberger, John I; Pistis, Giorgio; Streit, Fabian; Ursano, Robert J; Polimanti, Renato; Dennis, Michelle; Garrett, Melanie; Hair, Lauren; Harvey, Philip; Hauser, Elizabeth R; Hauser, Michael A; Huffman, Jennifer; Jacobson, Daniel; Madduri, Ravi; McMahon, Benjamin; Oslin, David W; Trafton, Jodie; Awasthi, Swapnil; Berrettini, Wade H; Bohus, Martin; Chang, Xiao; Chen, Hsi-Chung; Chen, Wei J; Christensen, Erik D; Crow, Scott; Duriez, Philibert; Edwards, Alexis C; Fernández-Aranda, Fernando; Galfalvy, Hanga; Gandal, Michael; Gorwood, Philip; Guo, Yiran; Hafferty, Jonathan D; Hakonarson, Hakon; Halmi, Katherine A; Hishimoto, Akitoyo; Jain, Sonia; Jamain, Stéphane; Jiménez-Murcia, Susana; Johnson, Craig; Kaplan, Allan S; Kaye, Walter H; Keel, Pamela K; Kennedy, James L; Kim, Minsoo; Klump, Kelly L; Levey, Daniel F; Li, Dong; Liao, Shih-Cheng; Lieb, Klaus; Lilenfeld, Lisa; Marshall, Christian R; Mitchell, James E; Okazaki, Satoshi; Otsuka, Ikuo; Pinto, Dalila; Powers, Abigail; Ramoz, Nicolas; Ripke, Stephan; Roepke, Stefan; Rozanov, Vsevolod; Scherer, Stephen W; Schmahl, Christian; Sokolowski, Marcus; Starnawska, Anna; Strober, Michael; Su, Mei-Hsin; Thornton, Laura M; Treasure, Janet; Ware, Erin B; Watson, Hunna J; Witt, Stephanie H; Woodside, D Blake; Yilmaz, Zeynep; Zillich, Lea; Adolfsson, Rolf; Agartz, Ingrid; Alda, Martin; Alfredsson, Lars; Appadurai, Vivek; Artigas, María Soler; Van der Auwera, Sandra; Azevedo, M Helena; Bass, Nicholas; Bau, Claiton HD; Baune, Bernhard T; Bellivier, Frank; Berger, Klaus; Biernacka, Joanna M; Bigdeli, Tim B; Binder, Elisabeth B; Boehnke, Michael; Boks, Marco P; Braff, David L; Bryant, Richard; Budde, Monika; Byrne, Enda M; Cahn, Wiepke; Castelao, Enrique; Cervilla, Jorge A; Chaumette, Boris; Corvin, Aiden; Craddock, Nicholas; Djurovic, Srdjan; Foo, Jerome C; Forstner, Andreas J; Frye, Mark; Gatt, Justine M; Giegling, Ina; Grabe, Hans J; Green, Melissa J; Grevet, Eugenio H; Grigoroiu-Serbanescu, Maria; Gutierrez, Blanca; Guzman-Parra, Jose; Hamshere, Marian L; Hartmann, Annette M; Hauser, Joanna; Heilmann-Heimbach, Stefanie; Hoffmann, Per; Ising, Marcus; Jones, Ian; Jones, Lisa A; Jonsson, Lina; Kahn, René S; Kelsoe, John R; Kendler, Kenneth S; Kloiber, Stefan; Koenen, Karestan C; Kogevinas, Manolis; Krebs, Marie-Odile; Landén, Mikael; Leboyer, Marion; Lee, Phil H; Levinson, Douglas F; Liao, Calwing; Lissowska, Jolanta; Mayoral, Fermin; McElroy, Susan L; McGrath, Patrick; McGuffin, Peter; McQuillin, Andrew; Mehta, Divya; Melle, Ingrid; Mitchell, Philip B; Molina, Esther; Morken, Gunnar; Nievergelt, Caroline; Nöthen, Markus M; O'Donovan, Michael C; Ophoff, Roel A; Owen, Michael J; Pato, Carlos; Pato, Michele T; Penninx, Brenda WJH; Potash, James B; Power, Robert A; Preisig, Martin; Quested, Digby; Ramos-Quiroga, Josep Antoni; Reif, Andreas; Ribasés, Marta; Richarte, Vanesa; Rietschel, Marcella; Rivera, Margarita; Roberts, Andrea; Roberts, Gloria; Rouleau, Guy A; Rovaris, Diego L; Sanders, Alan R; Schofield, Peter R; Schulze, Thomas G; Scott, Laura J; Serretti, Alessandro; Shi, Jianxin; Sirignano, Lea; Sklar, Pamela; Smeland, Olav B; Smoller, Jordan W; Sonuga-Barke, Edmund JS; Trzaskowski, Maciej; Tsuang, Ming T; Turecki, Gustavo; Vilar-Ribó, Laura; Vincent, John B; Völzke, Henry; Walters, James TR; Weickert, Cynthia Shannon; Weickert, Thomas W; Weissman, Myrna M; Williams, Leanne M; Wray, Naomi R; Zai, Clement C; Agerbo, Esben; Børglum, Anders D; Breen, Gerome; Demontis, Ditte; Erlangsen, Annette; Gelernter, Joel; Glatt, Stephen J; Hougaard, David M; Hwu, Hai-Gwo; Kuo, Po-Hsiu; Lewis, Cathryn M; Li, Qingqin S; Liu, Chih-Min; Martin, Nicholas G; McIntosh, Andrew M; Medland, Sarah E; Mors, Ole; Nordentoft, Merete; Olsen, Catherine M; Porteous, David; Smith, Daniel J; Stahl, Eli A; Stein, Murray B; Wasserman, Danuta; Werge, Thomas; Whiteman, David C; Willour, Virginia; VA Million Veteran Program (MVP); MVP Suicide Exemplar Workgroup; Suicide Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Eating Disorder Working Group of the Psychiatric Genomics Consortium; German Borderline Genomics Consortium; Coon, Hilary; Beckham, Jean C; Kimbrel, Nathan A; Ruderfer, Douglas M

    Objective

    Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.

    Methods

    This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.

    Results

    Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.

    Conclusions

    This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.