Author: "Michael A. Hauser" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Michael A. Hauser"' showing total 334 results

Start Over Author "Michael A. Hauser"

334 results on '"Michael A. Hauser"'

1. Genetic background determines severity of Loxl1-mediated systemic and ocular elastosis in mice

Author: Maria F. Suarez, Heather M. Schmitt, Megan S. Kuhn, TeddiJo Watkins, Kristyn M. Hake, Tara Weisz, Edward J. Flynn, Michael H. Elliott, Michael A. Hauser, and W. Daniel Stamer
Subjects: trabecular meshwork, lysyl oxidase, pseudoexfoliation syndrome, glaucoma, mechanical stress, Medicine, Pathology, RB1-214
Published: 2023
Full Text: View/download PDF

2. Large epigenome-wide association study identifies multiple novel differentially methylated CpG sites associated with suicidal thoughts and behaviors in veterans

Author: Nathan A. Kimbrel, Melanie E. Garrett, Mariah K. Evans, Clara Mellows, Michelle F. Dennis, Lauren P. Hair, Michael A. Hauser, the VA Mid-Atlantic MIRECC Workgroup, Allison E. Ashley-Koch, Jean C. Beckham, Patrick S. Calhoun, Eric Dedert, Eric B. Elbogen, John A. Fairbank, Robin A. Hurley, Jason D. Kilts, Angela Kirby, Sarah L. Martindale, Christine E. Marx, Scott D. McDonald, Scott D. Moore, Rajendra A. Morey, Jennifer C. Naylor, Jared Rowland, Robert D. Shura, Cindy Swinkels, Larry A. Tupler, Elizabeth E. Van Voorhees, and Ruth Yoash-Gantz
Subjects: suicide, epigenetics, methylation, psychiatry, suicidal ideation, Psychiatry, RC435-571
Abstract: IntroductionThe U.S. suicide mortality rate has steadily increased during the past two decades, particularly among military veterans; however, the epigenetic basis of suicidal thoughts and behaviors (STB) remains largely unknown.MethodsTo address this issue, we conducted an epigenome-wide association study of DNA methylation (DNAm) of peripheral blood samples obtained from 2,712 U.S. military veterans.ResultsThree DNAm probes were significantly associated with suicide attempts, surpassing the multiple testing threshold (FDR q-value
Published: 2023
Full Text: View/download PDF

3. Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR

Author: Alicia K. Smith, Andrew Ratanatharathorn, Adam X. Maihofer, Robert K. Naviaux, Allison E. Aiello, Ananda B. Amstadter, Allison E. Ashley-Koch, Dewleen G. Baker, Jean C. Beckham, Marco P. Boks, Evelyn Bromet, Michelle Dennis, Sandro Galea, Melanie E. Garrett, Elbert Geuze, Guia Guffanti, Michael A. Hauser, Seyma Katrinli, Varun Kilaru, Ronald C. Kessler, Nathan A. Kimbrel, Karestan C. Koenen, Pei-Fen Kuan, Kefeng Li, Mark W. Logue, Adriana Lori, Benjamin J. Luft, Mark W. Miller, Jane C. Naviaux, Nicole R. Nugent, Xuejun Qin, Kerry J. Ressler, Victoria B. Risbrough, Bart P. F. Rutten, Murray B. Stein, Robert J. Ursano, Eric Vermetten, Christiaan H. Vinkers, Lin Wang, Nagy A. Youssef, INTRuST Clinical Consortium, VA Mid-Atlantic MIRECC Workgroup, PGC PTSD Epigenetics Workgroup, Monica Uddin, and Caroline M. Nievergelt
Subjects: Science
Abstract: PTSD has been associated with DNA methylation of specific loci in the genome, but studies have been limited by small sample sizes. Here, the authors perform a meta-analysis of DNA methylation data from 10 different cohorts and identify CpGs in AHRR that are associated with PTSD.
Published: 2020
Full Text: View/download PDF

4. The social construction of genomics and genetic analysis in ocular diseases in Ibadan, South-western Nigeria

Author: Olusola Olawoye, Kabiru K. Salami, Abolaji Azeez, Precious Adebola, Tarela Sarimiye, John Imaledo, Tony Realini, Michael A. Hauser, and Adeyinka Ashaye
Subjects: Medicine, Science
Abstract: Genomics, an emerging field to improve public health practice, has potential benefits to understanding ocular diseases. This study explored the social construction of genomics in ocular diseases in the blind community in Ibadan, Nigeria, through two focus group discussions and twelve in-depth interview sessions conducted among people living with ocular disorders. The data were thematic and content-analysed. Although the participants had limited knowledge about ocular diseases, genomics, and their nexus, they maintained a positive attitude toward its potential benefits. This informed their willingness to participate in genomics testing for ocular diseases. The participants preferred saliva-based sample collection over blood-based, and expressed concern for the procedure and accrued benefits of genomics studies. Thus, public sensitisation about ocular diseases and client-centred genomics testing procedures should be engendered.
Published: 2022

5. Gene Expression Analysis in Three Posttraumatic Stress Disorder Cohorts Implicates Inflammation and Innate Immunity Pathways and Uncovers Shared Genetic Risk With Major Depressive Disorder

Author: Melanie E. Garrett, Xue Jun Qin, Divya Mehta, Michelle F. Dennis, Christine E. Marx, Gerald A. Grant, VA Mid-Atlantic MIRECC Workgroup, PTSD Initiative, Injury and Traumatic Stress (INTRuST) Clinical Consortium, Psychiatric Genomics Consortium PTSD Group, Murray B. Stein, Nathan A. Kimbrel, Jean C. Beckham, Michael A. Hauser, Allison E. Ashley-Koch, Mira Brancu, Patrick S. Calhoun, Eric Dedert, Eric B. Elbogen, John A. Fairbank, Robin A. Hurley, Jason D. Kilts, Angela Kirby, Sara Martindale, Scott D. McDonald, Scott D. Moore, Rajendra A. Morey, Jennifer C. Naylor, Jared Rowland, Robert Shura, Cindy Swinkels, Steven T. Szabo, Katherine H. Taber, Larry A. Tupler, Ruth E. Yoash-Gantz, Sarah McLeay, Wendy Harvey, Madeline Romaniuk, Darrell Crawford, David Colquhoun, Ross McD Young, Miriam Dwyer, John Gibson, Robyn O’Sullivan, Graham Cooksley, Christopher Strakosch, Rachel Thomson, Joanne Voisey, and Bruce Lawford
Subjects: posttraumatic stress disorder, gene expression, major depressive disorder, quantitative trait loci, multi-ethnic, meta-analysis, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Posttraumatic stress disorder (PTSD) is a complex psychiatric disorder that can develop following exposure to traumatic events. The Psychiatric Genomics Consortium PTSD group (PGC-PTSD) has collected over 20,000 multi-ethnic PTSD cases and controls and has identified both genetic and epigenetic factors associated with PTSD risk. To further investigate biological correlates of PTSD risk, we examined three PGC-PTSD cohorts comprising 977 subjects to identify differentially expressed genes among PTSD cases and controls. Whole blood gene expression was quantified with the HumanHT-12 v4 Expression BeadChip for 726 OEF/OIF veterans from the Veterans Affairs (VA) Mental Illness Research Education and Clinical Center (MIRECC), 155 samples from the Injury and Traumatic Stress (INTRuST) Clinical Consortium, and 96 Australian Vietnam War veterans. Differential gene expression analysis was performed in each cohort separately followed by meta-analysis. In the largest cohort, we performed co-expression analysis to identify modules of genes that are associated with PTSD and MDD. We then conducted expression quantitative trait loci (eQTL) analysis and assessed the presence of eQTL interactions involving PTSD and major depressive disorder (MDD). Finally, we utilized PTSD and MDD GWAS summary statistics to identify regions that colocalize with eQTLs. Although not surpassing correction for multiple testing, the most differentially expressed genes in meta-analysis were interleukin-1 beta (IL1B), a pro-inflammatory cytokine previously associated with PTSD, and integrin-linked kinase (ILK), which is highly expressed in brain and can rescue dysregulated hippocampal neurogenesis and memory deficits. Pathway analysis revealed enrichment of toll-like receptor (TLR) and interleukin-1 receptor genes, which are integral to cellular innate immune response. Co-expression analysis identified four modules of genes associated with PTSD, two of which are also associated with MDD, demonstrating common biological pathways underlying the two conditions. Lastly, we identified four genes (UBA7, HLA-F, HSPA1B, and RERE) with high probability of a shared causal eQTL variant with PTSD and/or MDD GWAS variants, thereby providing a potential mechanism by which the GWAS variant contributes to disease risk. In summary, we provide additional evidence for genes and pathways previously reported and identified plausible novel candidates for PTSD. These data provide further insight into genetic factors and pathways involved in PTSD, as well as potential regions of pleiotropy between PTSD and MDD.
Published: 2021
Full Text: View/download PDF

6. Examining Individual and Synergistic Contributions of PTSD and Genetics to Blood Pressure: A Trans-Ethnic Meta-Analysis

Author: Jennifer A. Sumner, Adam X. Maihofer, Vasiliki Michopoulos, Alex O. Rothbaum, Lynn M. Almli, Ole A. Andreassen, Allison E. Ashley-Koch, Dewleen G. Baker, Jean C. Beckham, Bekh Bradley, Gerome Breen, Jonathan R. I. Coleman, Anders M. Dale, Michelle F. Dennis, Norah C. Feeny, Carol E. Franz, Melanie E. Garrett, Charles F. Gillespie, Guia Guffanti, Michael A. Hauser, Sian M. J. Hemmings, Tanja Jovanovic, Nathan A. Kimbrel, William S. Kremen, Bruce R. Lawford, Mark W. Logue, Adriana Lori, Michael J. Lyons, Jessica Maples-Keller, Matig R. Mavissakalian, Regina E. McGlinchey, Divya Mehta, Rebecca Mellor, William Milberg, Mark W. Miller, Charles Phillip Morris, Matthew S. Panizzon, Kerry J. Ressler, Victoria B. Risbrough, Barbara O. Rothbaum, Peter Roy-Byrne, Soraya Seedat, Alicia K. Smith, Jennifer S. Stevens, Leigh Luella van den Heuvel, Joanne Voisey, Ross McD Young, Lori A. Zoellner, Caroline M. Nievergelt, and Erika J. Wolf
Subjects: posttraumatic stress disorder, genetics, blood pressure, trans-ethnic, meta-analysis, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European (n = 70,870) and African (n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: β = 2.83, standard error (SE) = 0.06, p < 1E-20; DBP: β = 1.32, SE = 0.04, p < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study – United Kingdom Biobank – PTSD symptoms were negatively associated with SBP levels (β = −1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (β = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (β = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (β = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk.
Published: 2021
Full Text: View/download PDF

7. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

Author: Caroline M. Nievergelt, Adam X. Maihofer, Torsten Klengel, Elizabeth G. Atkinson, Chia-Yen Chen, Karmel W. Choi, Jonathan R. I. Coleman, Shareefa Dalvie, Laramie E. Duncan, Joel Gelernter, Daniel F. Levey, Mark W. Logue, Renato Polimanti, Allison C. Provost, Andrew Ratanatharathorn, Murray B. Stein, Katy Torres, Allison E. Aiello, Lynn M. Almli, Ananda B. Amstadter, Søren B. Andersen, Ole A. Andreassen, Paul A. Arbisi, Allison E. Ashley-Koch, S. Bryn Austin, Esmina Avdibegovic, Dragan Babić, Marie Bækvad-Hansen, Dewleen G. Baker, Jean C. Beckham, Laura J. Bierut, Jonathan I. Bisson, Marco P. Boks, Elizabeth A. Bolger, Anders D. Børglum, Bekh Bradley, Megan Brashear, Gerome Breen, Richard A. Bryant, Angela C. Bustamante, Jonas Bybjerg-Grauholm, Joseph R. Calabrese, José M. Caldas- de- Almeida, Anders M. Dale, Mark J. Daly, Nikolaos P. Daskalakis, Jürgen Deckert, Douglas L. Delahanty, Michelle F. Dennis, Seth G. Disner, Katharina Domschke, Alma Dzubur-Kulenovic, Christopher R. Erbes, Alexandra Evans, Lindsay A. Farrer, Norah C. Feeny, Janine D. Flory, David Forbes, Carol E. Franz, Sandro Galea, Melanie E. Garrett, Bizu Gelaye, Elbert Geuze, Charles Gillespie, Aferdita Goci Uka, Scott D. Gordon, Guia Guffanti, Rasha Hammamieh, Supriya Harnal, Michael A. Hauser, Andrew C. Heath, Sian M. J. Hemmings, David Michael Hougaard, Miro Jakovljevic, Marti Jett, Eric Otto Johnson, Ian Jones, Tanja Jovanovic, Xue-Jun Qin, Angela G. Junglen, Karen-Inge Karstoft, Milissa L. Kaufman, Ronald C. Kessler, Alaptagin Khan, Nathan A. Kimbrel, Anthony P. King, Nastassja Koen, Henry R. Kranzler, William S. Kremen, Bruce R. Lawford, Lauren A. M. Lebois, Catrin E. Lewis, Sarah D. Linnstaedt, Adriana Lori, Bozo Lugonja, Jurjen J. Luykx, Michael J. Lyons, Jessica Maples-Keller, Charles Marmar, Alicia R. Martin, Nicholas G. Martin, Douglas Maurer, Matig R. Mavissakalian, Alexander McFarlane, Regina E. McGlinchey, Katie A. McLaughlin, Samuel A. McLean, Sarah McLeay, Divya Mehta, William P. Milberg, Mark W. Miller, Rajendra A. Morey, Charles Phillip Morris, Ole Mors, Preben B. Mortensen, Benjamin M. Neale, Elliot C. Nelson, Merete Nordentoft, Sonya B. Norman, Meaghan O’Donnell, Holly K. Orcutt, Matthew S. Panizzon, Edward S. Peters, Alan L. Peterson, Matthew Peverill, Robert H. Pietrzak, Melissa A. Polusny, John P. Rice, Stephan Ripke, Victoria B. Risbrough, Andrea L. Roberts, Alex O. Rothbaum, Barbara O. Rothbaum, Peter Roy-Byrne, Ken Ruggiero, Ariane Rung, Bart P. F. Rutten, Nancy L. Saccone, Sixto E. Sanchez, Dick Schijven, Soraya Seedat, Antonia V. Seligowski, Julia S. Seng, Christina M. Sheerin, Derrick Silove, Alicia K. Smith, Jordan W. Smoller, Scott R. Sponheim, Dan J. Stein, Jennifer S. Stevens, Jennifer A. Sumner, Martin H. Teicher, Wesley K. Thompson, Edward Trapido, Monica Uddin, Robert J. Ursano, Leigh Luella van den Heuvel, Miranda Van Hooff, Eric Vermetten, Christiaan H. Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Thomas Werge, Michelle A. Williams, Douglas E. Williamson, Sherry Winternitz, Christiane Wolf, Erika J. Wolf, Jonathan D. Wolff, Rachel Yehuda, Ross McD. Young, Keith A. Young, Hongyu Zhao, Lori A. Zoellner, Israel Liberzon, Kerry J. Ressler, Magali Haas, and Karestan C. Koenen
Subjects: Science
Abstract: Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.
Published: 2019
Full Text: View/download PDF

8. Genetic predictors of hippocampal subfield volume in PTSD cases and trauma-exposed controls

Author: Rajendra A. Morey, Melanie E. Garrett, Jennifer S. Stevens, Emily K. Clarke, Courtney C. Haswell, Sanne J.H. van Rooij, Negar Fani, Adriana Lori, Va Mid-Atlantic Mirecc Workgroup, Nathan A. Kimbrel, Michelle F. Dennis, Christine E. Marx, Jean C. Beckham, Gregory McCarthy, Michael A. Hauser, and Allison E. Ashley-Koch
Subjects: ptsd, childhood trauma, genetics, hippocampus, structural mri, hippocampal subfields, Psychiatry, RC435-571
Abstract: Behavioural, structural, and functional neuroimaging have implicated the hippocampus as a critical brain region in posttraumatic stress disorder (PTSD) pathogenesis. Recent work in a normative, primarily European, sample identified 15 unique genetic loci contributing to structural variability in six hippocampal subfield volumes. We explored the relevance of these loci in two samples (Mental Illness Research Education and Clinical Centre [MIRECC] and Grady; n = 290) of trauma-exposed individuals enriched for PTSD and of diverse ancestry. Four of the previous loci demonstrated nominal evidence of replication in the MIRECC dataset, primarily within non-Hispanic whites (NHW). One locus replicated in the Grady cohort, which was composed exclusively of non-Hispanic blacks (NHB). Our data supported genetic interactions with diagnosis of lifetime PTSD and genetic interactions with childhood trauma in the MIRECC sample, but not the Grady sample. Given the racial, diagnostic, and trauma-exposure differences with the original genome-wide association study (GWAS) report, we conducted a full GWAS in the MIRECC and Grady datasets. Interactions between genetic variants and lifetime PTSD or childhood trauma were interrogated for single nucleotide polymorphisms (SNPs) with evidence of main effects. Genetic associations surpassed false discovery rate (FDR)-correction within hippocampal subfields in fimbria, subiculum, cornu ammonis-1 (CA1), and hippocampal amygdala transition area (HATA). One association was replicated in the Grady cohort (rs12880795 in TUNAR with left (L)-HATA volume). The most significant association in the MIRECC dataset was between rs6906714 in LINC02571 and right (R)-fimbria volume (p = 5.99×10−8, q = 0.0056). Interestingly, the effect of rs6906714 on R-fimbria volume increased with exposure to childhood trauma (gene*environment [G*E] interaction p = 0.022). These preliminary results argue for G*E interactions between genetic loci with PTSD and childhood trauma on hippocampal phenotypes. Our results underscore the need for larger neuroimaging-genetic studies in PTSD, trauma, and ancestrally diverse populations.
Published: 2020
Full Text: View/download PDF

9. Lack of association between lysyl oxidase-like 1 polymorphisms and primary open angle glaucoma:a meta-analysis

Author: Wen Sun, Yan Sheng, Yu Weng, Chun-Xiao Xu, Susan E.I. Williams, Yu-Tao Liu, Michael A. Hauser, R. Rand Allingham, Ming-Juan Jin, and Guang-Di Chen
Subjects: glaucoma, gene polymorphism, meta-analysis, lysyl oxidase-like 1, Ophthalmology, RE1-994
Abstract: AIM: To study the associations between lysyl oxidase-like 1 (LOXL1) polymorphisms and primary open angle glaucoma (POAG) remain inconsistent. In this study, we have performed a meta-analysis to investigate the association of LOXL1 polymorphisms with POAG risk.METHODS: Published literature from PubMed and other databases were retrieved. All studies evaluating the association between LOXL1 polymorphisms (rs2165241, rs1048661, rs3825942) and POAG risk were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model.RESULTS: Twelve studies were identified as eligible articles, with thirteen (2098 cases and 16 473 controls), thirteen (1795 cases and 2916 controls) and sixteen population cohorts (2456 cases and 2846 controls) for the association of rs2165241, rs1048661 and rs3825942 with POAG risk respectively. Overall analyses showed no association between each LOXL1 polymorphism and POAG risk, and the negative associations were remained when the subjects were stratified as Caucasian and Asian. The heterozygote of rs2165241 was associated with reduced POAG risk in hospital-based populations (TC vs CC:OR, 0.79, 95%CI:0.63-0.99), and rs1048661 was associated with increased POAG risk in hospital-based populations in a dominant model (TT vs CC+CT:OR, 1.23, 95%CI:1.01-1.50); however, these associations were not found in population-based subjects.CONCLUSION: This meta-analysis suggests that LOXL1 polymorphisms are not associated with POAG risk. Given the limited sample size, the associations of LOXL1 polymorphisms with POAG risk in hospital-based populations await further investigation.
Published: 2014
Full Text: View/download PDF

10. Tests of the Efficient Markets Hypothesis

Author: Erhard Reschenhofer and Michael A. Hauser
Subjects: Probabilities. Mathematical statistics, QA273-280, Statistics, HA1-4737
Abstract: This paper surveys various statistical methods that have been proposed for the examination of the efficiency of financial markets and proposes a novel procedure for testing the predictability of a time series. For illustration, this procedure is applied to Austrian stock return series.
Published: 2016
Full Text: View/download PDF

11. Epigenome-wide association studies identify novel DNA methylation sites associated with PTSD: A meta-analysis of 23 military and civilian cohorts

Author: Onderzoek, Brain, MGGZ, Katrinli, Seyma, Wani, Agaz H, Maihofer, Adam X, Ratanatharathorn, Andrew, Daskalakis, Nikolaos P, Montalvo-Ortiz, Janitza, Núñez-Ríos, Diana L, Zannas, Anthony S, Zhao, Xiang, Aiello, Allison E, Ashley-Koch, Allison E, Avetyan, Diana, Baker, Dewleen G, Beckham, Jean C, Boks, Marco P, Brick, Leslie A, Bromet, Evelyn, Champagne, Frances A, Chen, Chia-Yen, Dalvie, Shareefa, Dennis, Michelle F, Fatumo, Segun, Fortier, Catherine, Galea, Sandro, Garrett, Melanie E, Geuze, Elbert, Grant, Gerald, Michael A Hauser, Hayes, Jasmeet P, Hemmings, Sian Mj, Huber, Bertrand Russel, Jajoo, Aarti, Jansen, Stefan, Kessler, Ronald C, Kimbrel, Nathan A, King, Anthony P, Kleinman, Joel E, Koen, Nastassja, Koenen, Karestan C, Kuan, Pei-Fen, Liberzon, Israel, Linnstaedt, Sarah D, Lori, Adriana, Luft, Benjamin J, Luykx, Jurjen J, Marx, Christine E, McLean, Samuel A, Rutten, Bart P F, Vermetten, Eric, Vinkers, Christiaan H, PGC-PTSD Epigenetics Workgroup, PsychENCODE PTSD Brainomics Project, Traumatic Stress Brain Research Group, Onderzoek, Brain, MGGZ, Katrinli, Seyma, Wani, Agaz H, Maihofer, Adam X, Ratanatharathorn, Andrew, Daskalakis, Nikolaos P, Montalvo-Ortiz, Janitza, Núñez-Ríos, Diana L, Zannas, Anthony S, Zhao, Xiang, Aiello, Allison E, Ashley-Koch, Allison E, Avetyan, Diana, Baker, Dewleen G, Beckham, Jean C, Boks, Marco P, Brick, Leslie A, Bromet, Evelyn, Champagne, Frances A, Chen, Chia-Yen, Dalvie, Shareefa, Dennis, Michelle F, Fatumo, Segun, Fortier, Catherine, Galea, Sandro, Garrett, Melanie E, Geuze, Elbert, Grant, Gerald, Michael A Hauser, Hayes, Jasmeet P, Hemmings, Sian Mj, Huber, Bertrand Russel, Jajoo, Aarti, Jansen, Stefan, Kessler, Ronald C, Kimbrel, Nathan A, King, Anthony P, Kleinman, Joel E, Koen, Nastassja, Koenen, Karestan C, Kuan, Pei-Fen, Liberzon, Israel, Linnstaedt, Sarah D, Lori, Adriana, Luft, Benjamin J, Luykx, Jurjen J, Marx, Christine E, McLean, Samuel A, Rutten, Bart P F, Vermetten, Eric, Vinkers, Christiaan H, and PGC-PTSD Epigenetics Workgroup, PsychENCODE PTSD Brainomics Project, Traumatic Stress Brain Research Group
Published: 2024

12. The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder

Author: Frank R. Wendt, Miguel Garcia-Argibay, Brenda Cabrera-Mendoza, Unnur A. Valdimarsdóttir, Joel Gelernter, Murray B. Stein, Michel G. Nivard, Adam X. Maihofer, Caroline M. Nievergelt, Henrik Larsson, Manuel Mattheisen, Renato Polimanti, Sandra M. Meier, Karmel W. Choi, Jonathan R.I. Coleman, Nikolaos P. Daskalakis, Christy A. Denckla, Elizabeth Ketema, Rajendra A. Morey, Andrew Ratanatharathorn, Katy Torres, Aliza P. Wingo, Clement C. Zai, Allison E. Aiello, Lynn M. Almli, Ananda B. Amstadter, Soren B. Andersen, Ole A. Andreassen, Paul A. Arbisi, Allison E. Ashley-Koch, S. Bryn Austin, Esmina Avdibegovic, Anders D. Borglum, Dragan Babic, Marie Bækvad-Hansen, Dewleen G. Baker, Jean C. Beckham, Laura J. Bierut, Jonathan I. Bisson, Marco P. Boks, Elizabeth A. Bolger, Bekh Bradley, Meghan Brashear, Gerome Breen, Richard A. Bryant, Angela C. Bustamante, Jonas Bybjerg-Grauholm, Joseph R. Calabrese, Jose Miguel Caldas-de-Almeida, Chia-Yen Chen, Anders M. Dale, Shareefa Dalvie, Jürgen Deckert, Douglas L. Delahanty, Michelle F. Dennis, Seth G. Disner, Katharina Domschke, Laramie E. Duncan, Alma Dzubur Kulenovic, Christopher R. Erbes, Alexandra Evans, Lindsay A. Farrer, Norah C. Feeny, Janine D. Flory, David Forbes, Carol E. Franz, Sandro Galea, Melanie E. Garrett, Aarti Gautam, Bizu Gelaye, Elbert Geuze, Charles F. Gillespie, Aferdita Goci Uka, Scott D. Gordon, Guia Guffanti, Rasha Hammamieh, Michael A. Hauser, Andrew C. Heath, Sian M.J. Hemmings, David Michael Hougaard, Miro Jakovljevic, Marti Jett, Eric Otto Johnson, Ian Jones, Tanja Jovanovic, Xue-Jun Qin, Karen-Inge Karstoft, Milissa L. Kaufman, Ronald C. Kessler, Alaptagin Khan, Nathan A. Kimbrel, Anthony P. King, Nastassja Koen, Henry R. Kranzler, William S. Kremen, Bruce R. Lawford, Lauren A.M. Lebois, Catrin Lewis, Israel Liberzon, Sarah D. Linnstaedt, Mark W. Logue, Adriana Lori, Bozo Lugonja, Jurjen J. Luykx, Michael J. Lyons, Jessica L. Maples-Keller, Charles Marmar, Nicholas G. Martin, Douglas Maurer, Matig R. Mavissakalian, Alexander McFarlane, Regina E. McGlinchey, Katie A. McLaughlin, Samuel A. McLean, Divya Mehta, Rebecca Mellor, Vasiliki Michopoulos, William Milberg, Mark W. Miller, Charles Phillip Morris, Ole Mors, Preben Bo Mortensen, Elliot C. Nelson, Merete Nordentoft, Sonya B. Norman, Meaghan O’Donnell, Holly K. Orcutt, Matthew S. Panizzon, Edward S. Peters, Alan L. Peterson, Matthew Peverill, Robert H. Pietrzak, Melissa A. Polusny, John P. Rice, Victoria B. Risbrough, Andrea L. Roberts, Alex O. Rothbaum, Barbara O. Rothbaum, Peter Roy-Byrne, Kenneth J. Ruggiero, Ariane Rung, Bart P.F. Rutten, Nancy L. Saccone, Sixto E. Sanchez, Dick Schijven, Soraya Seedat, Antonia V. Seligowski, Julia S. Seng, Christina M. Sheerin, Derrick Silove, Alicia K. Smith, Jordan W. Smoller, Scott R. Sponheim, Dan J. Stein, Jennifer S. Stevens, Martin H. Teicher, Wesley K. Thompson, Edward Trapido, Monica Uddin, Robert J. Ursano, Leigh Luella van den Heuvel, Miranda Van Hooff, Eric Vermetten, Christiaan Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Thomas Werge, Michelle A. Williams, Douglas E. Williamson, Sherry Winternitz, Christiane Wolf, Erika J. Wolf, Rachel Yehuda, Keith A. Young, Ross McD. Young, Hongyu Zhao, Lori A. Zoellner, Magali Haas, Heather Lasseter, Allison C. Provost, Rany M. Salem, Jonathan Sebat, Richard Shaffer, Tianying Wu, Stephan Ripke, Mark J. Daly, Kerry J. Ressler, Karestan C. Koenen, Biological Psychology, APH - Mental Health, APH - Methodology, Anatomy and neurosciences, Psychiatry, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: Genome-wide association study, Epidemiology, Siblings, PTSD, Mendelian Randomization Analysis, Comorbidities, SDG 3 - Good Health and Well-being, Humans, ADHD, Attention Deficit Disorder with Hyperactivity/epidemiology, Stress Disorders, Post-Traumatic/genetics, Biological Psychiatry, Causal inference
Abstract: Background: Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are associated, but it is unclear if this is a causal relationship or confounding. We used genetic analyses and sibling comparisons to clarify the direction of this relationship. Methods: Linkage disequilibrium score regression and 2-sample Mendelian randomization were used to test for genetic correlation (r g) and bidirectional causal effects using European ancestry genome-wide association studies of ADHD (20,183 cases and 35,191 controls) and 6 PTSD definitions (up to 320,369 individuals). Several additional variables were included in the analysis to verify the independence of the ADHD-PTSD relationship. In a population-based sibling comparison (N = 2,082,118 individuals), Cox regression models were fitted to account for time at risk, a range of sociodemographic factors, and unmeasured familial confounders (via sibling comparisons). Results: ADHD and PTSD had consistent r g (r g range, 0.43–0.52; p < .001). ADHD genetic liability was causally linked with increased risk for PTSD (β = 0.367; 95% CI, 0.186–0.552; p = 7.68 × 10 −5). This result was not affected by heterogeneity, horizontal pleiotropy (Mendelian randomization Egger intercept = 4.34 × 10 −4, p = .961), or other phenotypes and was consistent across PTSD datasets. However, we found no consistent associations between PTSD genetic liability and ADHD risk. Individuals diagnosed with ADHD were at a higher risk for developing PTSD than their undiagnosed sibling (hazard ratio = 2.37; 95% CI, 1.98–3.53). Conclusions: Our findings add novel evidence supporting the need for early and effective treatment of ADHD, as patients with this diagnosis are at significantly higher risk to develop PTSD later in life.
Published: 2023

13. Direct Risk Assessment From Myocardial Perfusion Imaging Using Explainable Deep Learning

Author: Ananya Singh, Robert J.H. Miller, Yuka Otaki, Paul Kavanagh, Michael T. Hauser, Evangelos Tzolos, Jacek Kwiecinski, Serge Van Kriekinge, Chih-Chun Wei, Tali Sharir, Andrew J. Einstein, Mathews B. Fish, Terrence D. Ruddy, Philipp A. Kaufmann, Albert J. Sinusas, Edward J. Miller, Timothy M. Bateman, Sharmila Dorbala, Marcelo Di Carli, Joanna X. Liang, Cathleen Huang, Donghee Han, Damini Dey, Daniel S. Berman, Piotr J. Slomka, and University of Zurich
Subjects: 610 Medicine & health, Radiology, Nuclear Medicine and imaging, 10181 Clinic for Nuclear Medicine, Cardiology and Cardiovascular Medicine
Abstract: Myocardial perfusion imaging (MPI) is frequently used to provide risk stratification, but methods to improve the accuracy of these predictions are needed.We developed an explainable deep learning (DL) model (HARD MACE [major adverse cardiac events]-DL) for the prediction of death or nonfatal myocardial infarction (MI) and validated its performance in large internal and external testing groups.Patients undergoing single-photon emission computed tomography MPI were included, with 20,401 patients in the training and internal testing group (5 sites) and 9,019 in the external testing group (2 different sites). HARD MACE-DL uses myocardial perfusion, motion, thickening, and phase polar maps combined with age, sex, and cardiac volumes. The primary outcome was all-cause mortality or nonfatal MI. Prognostic accuracy was evaluated using area under the receiver-operating characteristic curve (AUC).During internal testing, patients with normal perfusion and elevated HARD-MACE-DL risk were at higher risk than patients with abnormal perfusion and low HARD-MACE-DL risk (annualized event rate, 2.9% vs 1.2%; P 0.001). Patients in the highest quartile of HARD MACE-DL score had an annual rate of death or MI (4.8%) 10-fold higher than patients in the lowest quartile (0.48% per year). In external testing, the AUC for HARD MACE-DL (0.73; 95% CI: 0.71-0.75) was higher than a logistic regression model (AUC: 0.70), stress TPD (AUC: 0.65), and ischemic TPD (AUC: 0.63; all P 0.01). Calibration, a measure of how well predicted risk matches actual risk, was excellent in both groups (Brier score, 0.079 for internal and 0.070 for external).The DL model predicts death or MI directly from MPI, by estimating patient-level risk with good calibration and improved accuracy compared with traditional quantitative approaches. The model incorporates mechanisms to explain to the physician which image regions contribute to the adverse event prediction.
Published: 2023

14. Rare protective variants and glaucoma-relevant cell stressors modulate angiopoietin-like 7 expression

Author: Inas F Aboobakar, Edward Ryan A Collantes, Michael A Hauser, W Daniel Stamer, and Janey L Wiggs
Subjects: Genetics, General Medicine, Molecular Biology, Genetics (clinical)
Abstract: Rare missense and nonsense variants in the Angiopoietin-like 7 (ANGPTL7) gene confer protection from primary open-angle glaucoma (POAG), though the functional mechanism remains uncharacterized. Interestingly, larger variant effect size strongly correlates with in silico predictions of increased protein instability (r = −0.98), suggesting that protective variants lower Angptl7 protein levels. Here, we show that missense and nonsense variants cause aggregation of mutant Angptl7 protein in the endoplasmic reticulum (ER) and decreased levels of secreted protein in human trabecular meshwork (TM) cells; a lower secreted:intracellular protein ratio strongly correlates with variant effects on intraocular pressure (r = 0.81). Importantly, accumulation of mutant protein in the ER does not increase expression of ER stress proteins in TM cells (p > 0.05 for all variants tested). Cyclic mechanical stress, a glaucoma-relevant physiologic stressor, also significantly lowers ANGPTL7 expression in primary cultures of human Schlemm’s canal cells (−2.4 fold-change, p = 0.01). Collectively, these data suggest that the protective effects of ANGPTL7 variants in POAG stem from lower levels of secreted protein, which may modulate responses to physiologic and pathologic ocular cell stressors. Downregulation of ANGPTL7 expression may therefore serve as a viable preventative and therapeutic strategy for this common, blinding disease.
Published: 2023

15. Mitochondrial TXNRD2 and ME3 Genetic Risk Scores Are Associated with Specific Primary Open-Angle Glaucoma Phenotypes

Author: Inas F. Aboobakar, Tyler G. Kinzy, Yan Zhao, Baojian Fan, Louis R. Pasquale, Ayub Qassim, Antonia Kolovos, Joshua M. Schmidt, Jamie E. Craig, Jessica N. Cooke Bailey, Janey L. Wiggs, R. Rand Allingham, Murray Brilliant, Donald L. Budenz, John H. Fingert, Douglas Gaasterland, Teresa Gaasterland, Jonathan L. Haines, Michael A. Hauser, Richard K. Lee, Paul R. Lichter, Yutao Liu, Syoko Moroi, Jonathan Myers, Margaret Pericak-Vance, Anthony Realini, Doug Rhee, Julia E. Richards, Robert Ritch, Joel S. Schuman, William K. Scott, Kuldev Singh, Arthur J. Sit, Douglas Vollrath, Robert N. Weinreb, Gadi Wollstein, and Donald J. Zack
Subjects: Ophthalmology
Published: 2023

16. A Dynamically Stabilized Recurrent Neural Network

Author: Samer S. Saab, Asok Ray, Michael A. Hauser, and Yiwei Fu
Subjects: Recurrent neural network, Artificial Intelligence, Computer Networks and Communications, business.industry, Computer science, General Neuroscience, Artificial intelligence, business, Software
Published: 2021

17. Eyes of Africa: The Genetics of Blindness: Study Design and Methodology

Author: CM Chuka-Okosa, Tony Realini, Onoja Akpa, Olusola Olawoye, Michael A. Hauser, and Adeyinka O. Ashaye
Subjects: 0301 basic medicine, Glaucoma, Locus (genetics), Genome-wide association study, Blindness, Study Protocol, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Genetics, Humans, Medicine, Genetic Predisposition to Disease, Human heredity, Exome sequencing, Adaptor Proteins, Signal Transducing, business.industry, Case-control study, Methodology, General Medicine, RE1-994, medicine.disease, Ophthalmology, 030104 developmental biology, Case-Control Studies, Africa, 030221 ophthalmology & optometry, Mendelian inheritance, symbols, business, Glaucoma, Open-Angle, Genome-Wide Association Study
Abstract: Background This report describes the design and methodology of the “Eyes of Africa: The Genetics of Blindness,” a collaborative study funded through the Human Heredity and Health in Africa (H3Africa) program of the National Institute of Health. Methods This is a case control study that is collecting a large well phenotyped data set among glaucoma patients and controls for a genome wide association study. (GWAS). Multiplex families segregating Mendelian forms of early-onset glaucoma will also be collected for exome sequencing. Discussion A total of 4500 cases/controls have been recruited into the study at the end of the 3rd funded year of the study. All these participants have been appropriately phenotyped and blood samples have been received from these participants. Recent GWAS of POAG in African individuals demonstrated genome-wide significant association with the APBB2 locus which is an association that is unique to individuals of African ancestry. This study will add to the existing knowledge and understanding of POAG in the African population.
Published: 2021

18. Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Author: Alma Dzubur Kulenovic, Michael J. Lyons, Elizabeth A. Bolger, Kenneth J. Ruggiero, Zhewu Wang, Laramie E. Duncan, Bozo Lugonja, Joanne Voisey, José Miguel Caldas-de-Almeida, Regina E. McGlinchey, Laura J. Bierut, Michael A. Hauser, Jean C. Beckham, Dan J. Stein, Alexander C. McFarlane, Elbert Geuze, Victoria B. Risbrough, Douglas Maurer, Christy A. Denckla, Seth G. Disner, William P. Milberg, Erika J. Wolf, Scott R. Sponheim, Caroline M. Nievergelt, Henry R. Kranzler, Clement C. Zai, Antonia V. Seligowski, Miro Jakovljević, Katharina Domschke, Paul A. Arbisi, Thomas Werge, Vasiliki Michopoulos, Joel Gelernter, Sarah D. Linnstaedt, Nastassja Koen, Sonya B. Norman, Nicholas G. Martin, Janine D. Flory, Meghan M Brashear, Melissa A. Polusny, Nathan A. Kimbrel, Douglas L. Delahanty, Milissa L. Kaufman, Peter Roy-Byrne, Magali Haas, Monica Uddin, Matig R. Mavissakalian, William S. Kremen, Ole A. Andreassen, Marco P. Boks, Matthew S. Panizzon, Christiaan H. Vinkers, Bart P. F. Rutten, Heather Lasseter, Richard A. Shaffer, Aferdita Goci, Jessica L. Maples-Keller, Israel Liberzon, Melanie E. Garrett, Alicia K. Smith, Catrin Lewis, Dewleen G. Baker, Murray B. Stein, Xuejun Qin, Nikolaos P. Daskalakis, Sherry Winternitz, Douglas E. Williamson, Alex O. Rothbaum, David Forbes, Leigh van den Heuvel, Scott D. Gordon, Edward J. Trapido, Marti Jett, Ole Mors, Adam X. Maihofer, Christina M. Sheerin, Lori A. Zoellner, A.C. Bustamante, David M. Hougaard, Alexandra Evans, Chia-Yen Chen, Robert H. Pietrzak, Rachel Yehuda, Allison C. Provost, Matthew Peverill, Aarti Gautam, Bruce R. Lawford, Derrick Silove, Bekh Bradley, Gerome Breen, Charles F. Gillespie, Allison E. Ashley-Koch, Kerry J. Ressler, Christiane Wolf, Renato Polimanti, Jonathan Ian Bisson, Adriana Lori, Lynn M. Almli, Norah C. Feeny, Jonas Bybjerg-Grauholm, Guia Guffanti, Søren Bo Andersen, Anders D. Børglum, Elizabeth Ketema, Andrea L. Roberts, Marie Bμkvad-Hansen, Ross McD. Young, Jürgen Deckert, Jonathan Sebat, Rajendra A. Morey, P. B. Mortensen, Lindsay A. Farrer, Yunpeng Wang, Karestan C. Koenen, Joseph R. Calabrese, Bizu Gelaye, Jurjen J. Luykx, Andrew Ratanatharathorn, Charles P. Morris, S. Bryn Austin, Miranda Van Hooff, Edward S. Peters, Katie A. McLaughlin, Anthony P. King, Jonathan R. I. Coleman, Holly K. Orcutt, Keith A. Young, Samuel A. McLean, Jennifer S. Stevens, Rasha Hammamieh, Robert J. Ursano, Mark W. Miller, Allison E. Aiello, Charles R. Marmar, Esmina Avdibegović, Katy Torres, Elliot C. Nelson, Rany M. Salem, Martin H. Teicher, Rebecca Mellor, Karen-Inge Karstoft, Aliza P. Wingo, Alaptagin Khan, Michelle A. Williams, Dick Schijven, Merete Nordentoft, Ananda B. Amstadter, Shareefa Dalvie, Michelle F. Dennis, Mark J. Daly, Mark W. Logue, Soraya Seedat, Julia S. Seng, Carol E. Franz, Stephan Ripke, Karmel W. Choi, Sandro Galea, Richard A. Bryant, Ian Jones, Anders M. Dale, Wesley K. Thompson, Lauren A.M. Lebois, Sixto E. Sanchez, Ronald C. Kessler, Tanja Jovanovic, Divya Mehta, Jordan W. Smoller, Eric O. Johnson, John P. Rice, Andrew C. Heath, Nancy L. Saccone, Barbara O. Rothbaum, Alan L. Peterson, Meaghan O'Donnell, Sian M. J. Hemmings, Eric Vermetten, Dragan Babić, Hongyu Zhao, Tianying Wu, Christopher R. Erbes, Ariane Rung, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Centro de Estudos de Doenças Crónicas (CEDOC), Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, MUMC+: MA Psychiatrie (3), Anatomy and neurosciences, Psychiatry, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: Oncology, Multivariate analysis, LD SCORE REGRESSION, Genome-wide association study, THOUSANDS, Medical and Health Sciences, Stress Disorders, Post-Traumatic, GWAS, Stress Disorders, Psychiatry, Genome-Wide Association Study / methods, Traumatic stress, PROLIFERATION, PTSD, Single Nucleotide, Biological Sciences, Post-Traumatic Stress Disorder (PTSD), Anxiety Disorders, Mental Health, Phenotype, Cohort, Polymorphism, Single Nucleotide / genetics, medicine.medical_specialty, Stress Disorders, Post-Traumatic / genetics, Quantitative trait locus, Polymorphism, Single Nucleotide, Genetic correlation, behavioral disciplines and activities, Trauma, Heritability, Internal medicine, PSYCHIATRIC GENOMICS, mental disorders, medicine, Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, METAANALYSIS, Biological Psychiatry, Genetic association, business.industry, Prevention, Human Genome, Psychology and Cognitive Sciences, PheWAS, Brain Disorders, Post-Traumatic, RISK-FACTORS, business, Genome-Wide Association Study
Abstract: Funding Information: This work was supported by the National Institute of Mental Health / U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium ), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience . Statistical analyses were carried out on the LISA/Genetic Cluster Computer ( https://userinfo.surfsara.nl/systems/lisa ) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. Funding Information: MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc., RallyPoint Networks, Inc., Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled “Genotype-guided dosing of opioid agonists,” filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the National Institute of Mental Health/ U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience. Statistical analyses were carried out on the LISA/Genetic Cluster Computer (https://userinfo.surfsara.nl/systems/lisa) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. This material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the U.S. Department of the Army or the Department of Defense. We thank the investigators who comprise the PGC-PTSD working group and especially the more than 206,000 research participants worldwide who shared their life experiences and biological samples with PGC-PTSD investigators. We thank Mark Zervas for his critical input. Full acknowledgments are in Supplement 1. MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc. RallyPoint Networks, Inc. Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled ?Genotype-guided dosing of opioid agonists,? filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2021 Society of Biological Psychiatry Background: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods. publishersversion published
Published: 2022

19. Integral role for lysyl oxidase‐like‐1 in conventional outflow tissue function and behavior

Author: W. Daniel Stamer, Michael A. Hauser, Guorong Li, William M. Johnson, Maria Gomez-Caraballo, Jenny Cui, Todd L. Fleming, Iris Navarro, Heather Schmitt, Chanyoung Lee, C. Ross Ethier, Sina Farsiu, Joseph M. Sherwood, and Michael H. Elliott
Subjects: 0301 basic medicine, medicine.medical_specialty, Intraocular pressure, genetic structures, Ocular hypertension, Exfoliation Syndrome, Biochemistry, Article, Conventional outflow, Extracellular matrix, Mice, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Ophthalmology, Genetics, medicine, Animals, Homeostasis, Molecular Biology, Intraocular Pressure, Schlemm's canal, biology, business.industry, Glaucoma, medicine.disease, eye diseases, Extracellular Matrix, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, biology.protein, Ocular Hypertension, Amino Acid Oxidoreductases, sense organs, business, Elastin, 030217 neurology & neurosurgery, Biotechnology
Abstract: Lysyl oxidase like-1 (LOXL1), a vital crosslinking enzyme in elastin fiber maintenance, is essential for the stability and strength of elastic vessels and tissues. Variants in the LOXL1 locus associate with a dramatic increase in risk of exfoliation syndrome, a systemic fibrillopathy, which often presents with ocular hypertension and exfoliation glaucoma. We examined the role of LOXL1 in conventional outflow function, the prime regulator of intraocular pressure. Using Loxl1(−/−), Loxl1(+/−) and Loxl1(+/+) mice, we observed an inverse relationship between LOXL1 expression and intraocular pressure, which worsened with age. Elevated intraocular pressure in Loxl1(−/−) mice was associated with a larger globe, decreased ocular compliance, increased outflow facility, extracellular matrix abnormalities, and dilated intrascleral veins, yet no dilation of arteries or capillaries. Interestingly, in living Loxl1(−/−) mouse eyes, Schlemm’s canal was less susceptible to collapse when challenged with acute elevations in intraocular pressure, suggesting elevated episcleral venous pressure. Thus, LOXL1 expression is required for normal intraocular pressure control, while ablation results in altered extracellular matrix repair/homeostasis and conventional outflow physiology. Dilation of Schlemm’s canal and distal veins, but not arteries, is consistent with key structural and functional roles for elastin in low-pressure vessels subjected to cyclical mechanical stress.
Published: 2020

20. Impact of traumatic life events and polygenic risk scores for major depression and posttraumatic stress disorder on Iraq/Afghanistan Veterans

Author: Rachele K. Lipsky, Melanie E. Garrett, Michelle F. Dennis, Michael A. Hauser, Jean C. Beckham, Allison E. Ashley-Koch, and Nathan A. Kimbrel
Subjects: Psychiatry and Mental health, Biological Psychiatry
Abstract: Traumatic experiences and genetic heritability are among the most widely acknowledged risk factors leading to the development of psychopathology; including posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). The purpose of this study was to investigate if polygenic risk scores (PRS) among Veterans interacted with traumatic stress to predict PTSD and MDD. 1,389 Iraq-Afghanistan military service Veterans from the Mental Illness Research Education and Clinical Center dataset were analyzed. Genome-wide association study (GWAS) statistics were utilized to generate PRS for PTSD (PRS
Published: 2022

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

Author: Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Caroline Hayward, Andrew C. Heath, Glyn Lewis, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Sara A. Paciga, Nancy L. Pedersen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Hreinn Stefansson, Stacy Steinberg, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Roy H. Perlis, David J. Porteous, Catherine Schaefer, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Patrick F. Sullivan, Kevin S. O’Connell, Brandon Coombes, Zhen Qiao, Thomas D. Als, Sigrid Børte, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Verneri Antilla, Anastasia Antoniou, Ji Hyun Baek, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Erlend Bøen, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Ian R. Gizer, Katherine Gordon-Smith, Tiffany A. Greenwood, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Peter A. Holmans, Laura Huckins, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, Sarah Kittel-Schneider, Maria Koromina, Thorsten M. Kranz, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Markus Leber, Heon-Jeong Lee, Shawn E. Levy, Catrin Lewis, Martin Lundberg, Sigurdur H. Magnusson, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Nathaniel W. McGregor, James D. McKay, Helena Medeiros, Vincent Millischer, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, Fabio Rivas, Julian Roth, Panos Roussos, Fanny Senner, Sally Sharp, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, Chikashi Terao, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, null HUNT All-In Psychiatry, Gulja Babadjanova, Lena Backlund, Susanne Bengesser, Douglas H.R. Blackwood, Vaughan J. Carr, Stanley Catts, Dimitris Dikeos, Bruno Etain, Panagiotis Ferentinos, Micha Gawlik, Elliot S. Gershon, Frans Henskens, Jan Hillert, Kyung Sue Hong, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, George Kirov, Christine Lochner, Carmel Loughland, Carol A. Mathews, Francis J. McMahon, Patricia Michie, Bryan Mowry, Benjamin M. Neale, Caroline M. Nievergelt, Ketil J. Oedegaard, Tomas Olsson, Chris Pantelis, George P. Patrinos, Eva Z. Reininghaus, Takeo Saito, Ulrich Schall, Martin Schalling, Rodney J. Scott, Eystein Stordal, Arne E. Vaaler, Eduard Vieta, Irwin D. Waldman, John-Anker Zwart, John I. Nurnberger, Arianna Di Florio, Roger A.H. Adan, Tetsuya Ando, Harald Aschauer, Jessica H. Baker, Vladimir Bencko, Andreas Birgegård, Joseph M. Boden, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Laura Carlberg, Matteo Cassina, Maurizio Clementi, Roger D. Cone, Philippe Courtet, James J. Crowley, Unna N. Danner, Oliver S.P. Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M. Dick, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo Martinez, Laramie E. Duncan, Karin Egberts, Morten Mattingsdal, Sara McDevitt, Ingrid Meulenbelt, Nadia Micali, James Mitchell, Karen Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Melissa A. Munn-Chernoff, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K. O’Toole, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papezova, Richard Parker, John F. Pearson, Stefan Ehrlich, Geòrgia Escaramís, Thomas Espeseth, Xavier Estivill, Anne Farmer, Angela Favaro, Krista Fischer, James A.B. Floyd, Manuel Föcker, Lenka Foretova, Monica Forzan, Christopher S. Franklin, Giovanni Gambaro, Johanna Giuranna, Paola Giusti-Rodríquez, Fragiskos Gonidakis, Scott Gordon, Monica Gratacos Mayora, Sébastien Guillaume, Ken B. Hanscombe, Konstantinos Hatzikotoulas, Johannes Hebebrand, Sietske G. Helder, Anjali K. Henders, Beate Herpertz-Dahlmann, Wolfgang Herzog, Anke Hinney, L. John Horwood, Christopher Hübel, Liselotte V. Petersen, Kirstin L. Purves, Anu Raevuori, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Filip Rybakowski, Paolo Santonastaso, André Scherag, Ulrike Schmidt, Nicholas J. Schork, Alexandra Schosser, Jochen Seitz, Lenka Slachtova, P. Eline Slagboom, Margarita C.T. Slof-Op ‘t Landt, Agnieszka Slopien, Nicole Soranzo, Sandro Sorbi, Lorraine Southam, Vidar W. Steen, Laura M. Huckins, James I. Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimir Janout, Jennifer Jordan, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien J.H. Kas, Martin A. Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl-Ri Kim, Katherine M. Kirk, Lars Klareskog, Gun Peggy S. Knudsen, Janne T. Larsen, Stephanie Le Hellard, Virpi M. Leppä, Paul Lichtenstein, Bochao Danae Lin, Astri Lundervold, Jurjen Luykx, Mario Maj, Katrin Mannik, Sara Marsal, Garret D. Stuber, Jin P. Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A. van Elburg, Eric F. van Furth, Tracey D. Wade, Gudrun Wagner, Esther Walton, H. Erich Wichmann, Elisabeth Widen, Shuyang Yao, Eleftheria Zeggini, Stephanie Zerwas, Stephan Zipfel, Martin Jungkunz, Lydie Dietl, Cornelia E. Schwarze, Norbert Dahmen, Björn H. Schott, Arian Mobascher, Silvia Crivelli, Michelle F. Dennis, Phillip D. Harvey, Bruce W. Carter, Jennifer E. Huffman, Daniel Jacobson, Ravi Madduri, Maren K. Olsen, John Pestian, J. Michael Gaziano, Sumitra Muralidhar, Rachel Ramoni, Jean Beckham, Kyong-Mi Chang, Christopher J. O’Donnell, Philip S. Tsao, James Breeling, Grant Huang, J.P. Casas Romero, Jennifer Moser, Stacey B. Whitbourne, Jessica V. Brewer, Mihaela Aslan, Todd Connor, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Luis E. Selva, Nhan Do, Shahpoor Shayan, Kelly Cho, Saiju Pyarajan, Elizabeth Hauser, Yan Sun, Hongyu Zhao, Peter Wilson, Rachel McArdle, Louis Dellitalia, Kristin Mattocks, John Harley, Clement J. Zablocki, Jeffrey Whittle, Frank Jacono, Salvador Gutierrez, Gretchen Gibson, Kimberly Hammer, Laurence Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Roy Mathew, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, Douglas Ivins, Stephen Mastorides, Jonathan Moorman, Saib Gappy, Jon Klein, Nora Ratcliffe, Hermes Florez, Olaoluwa Okusaga, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Neeraj Tandon, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, Suthat Liangpunsakul, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Joseph Constans, Paul Meyer, Jennifer Greco, Michael Rauchman, Richard Servatius, Melinda Gaddy, Agnes Wallbom, Timothy Morgan, Todd Stapley, Scott Sherman, George Ross, Philip Tsao, Patrick Strollo, Edward Boyko, Laurence Meyer, Samir Gupta, Mostaqul Huq, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, Robert Striker, Dietl, Lydie, Schwarze, Cornelia E., Dahmen, Norbert, Schott, Björn H., Nöthen, Markus M., Ripke, Stephan, Mobascher, Arian, Rujescu, Dan, Lieb, Klaus, Roepke, Stefan, Schmahl, Christian, Bohus, Martin, Rietschel, Marcella, Crivelli, Silvia, Dennis, Michelle F., Harvey, Phillip D., Carter, Bruce W., Huffman, Jennifer E., Jacobson, Daniel, Madduri, Ravi, Olsen, Maren K., Pestian, John, Gaziano, J. Michael, Muralidhar, Sumitra, Ramoni, Rachel, Beckham, Jean, Chang, Kyong-Mi, O'Donnell, Christopher J., Tsao, Philip S., Breeling, James, Huang, Grant, Romero, J. P. Casas, Moser, Jennifer, Whitbourne, Stacey B., Brewer, Jessica V., Aslan, Mihaela, Connor, Todd, Argyres, Dean P., Stephens, Brady, Brophy, Mary T., Humphries, Donald E., Selva, Luis E., Do, Nhan, Shayan, Shahpoor, Cho, Kelly, Pyarajan, Saiju, Hauser, Elizabeth, Sun, Yan, Zhao, Hongyu, Wilson, Peter, McArdle, Rachel, Dellitalia, Louis, Mattocks, Kristin, Harley, John, Zablocki, Clement J., Whittle, Jeffrey, Jacono, Frank, Gutierrez, Salvador, Gibson, Gretchen, Hammer, Kimberly, Kaminsky, Laurence, Villareal, Gerardo, Kinlay, Scott, Xu, Junzhe, Hamner, Mark, Mathew, Roy, Bhushan, Sujata, Iruvanti, Pran, Godschalk, Michael, Ballas, Zuhair, Ivins, Douglas, Mastorides, Stephen, Moorman, Jonathan, Gappy, Saib, Klein, Jon, Ratcliffe, Nora, Florez, Hermes, Okusaga, Olaoluwa, Murdoch, Maureen, Sriram, Peruvemba, Yeh, Shing Shing, Tandon, Neeraj, Jhala, Darshana, Aguayo, Samuel, Cohen, David, Sharma, Satish, Liangpunsakul, Suthat, Oursler, Kris Ann, Whooley, Mary, Ahuja, Sunil, Constans, Joseph, Meyer, Paul, Greco, Jennifer, Rauchman, Michael, Servatius, Richard, Gaddy, Melinda, Wallbom, Agnes, Morgan, Timothy, Stapley, Todd, Sherman, Scott, Ross, George, Tsao, Philip, Strollo, Patrick, Boyko, Edward, Meyer, Laurence, Gupta, Samir, Huq, Mostaqul, Fayad, Joseph, Hung, Adriana, Lichy, Jack, Hurley, Robin, Robey, Brooks, Striker, Robert, Wray, Naomi R., Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F. M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T. F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R. I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E. J. C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O'Reilly, Paul F., Oskarsson, Hogni, Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A. F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C. B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Penninx, Brenda W. J. H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., O'Connell, Kevin S., Coombes, Brandon, Qiao, Zhen, Als, Thomas D., Børte, Sigrid, Charney, Alexander W., Drange, Ole Kristian, Gandal, Michael J., Hagenaars, Saskia P., Ikeda, Masashi, Kamitaki, Nolan, Kim, Minsoo, Krebs, Kristi, Panagiotaropoulou, Georgia, Schilder, Brian M., Sloofman, Laura G., Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Bøen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsåshagen, Torbjørn, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frei, Oleksandr, Freimer, Nelson B., Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Gizer, Ian R., Gordon-Smith, Katherine, Greenwood, Tiffany A., Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Holmans, Peter A., Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Kogevinas, Manolis, Koromina, Maria, Kranz, Thorsten M., Kranzler, Henry R., Kubo, Michiaki, Kupka, Ralph, Kushner, Steven A., Lavebratt, Catharina, Lawrence, Jacob, Leber, Markus, Lee, Heon-Jeong, Lee, Phil H., Levy, Shawn E., Lewis, Catrin, Liao, Calwing, Lundberg, Martin, Magnusson, Sigurdur H., Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, McGregor, Nathaniel W., McKay, James D., Medeiros, Helena, Millischer, Vincent, Moran, Jennifer L., Morris, Derek W., Mühleisen, Thomas W., O'Brien, Niamh, O'Donovan, Claire, Olde Loohuis, Loes M., Oruc, Lilijana, Papiol, Sergi, Pardiñas, Antonio F., Perry, Amy, Pfennig, Andrea, Porichi, Evgenia, Quested, Digby, Raj, Towfique, Rapaport, Mark H., Regeer, Eline J., Rivas, Fabio, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sánchez-Mora, Cristina, Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Sobell, Janet L., Artigas, Maria Soler, Spijker, Anne T., Stein, Dan J., Strauss, John S., Świątkowska, Beata, Terao, Chikashi, Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Xi, Simon, Xu, Wei, Kay Yang, Jessica Mei, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dikeos, Dimitris, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen V., Kahn, René S., Kelsoe, John R., Kirov, George, Landén, Mikael, Leboyer, Marion, Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Mitchell, Philip B., Morken, Gunnar, Mowry, Bryan, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Oedegaard, Ketil J., Olsson, Tomas, Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Weickert, Cynthia Shannon, Stordal, Eystein, Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Zwart, John-Anker, Biernacka, Joanna M., Nurnberger, John I., Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., Andreassen, Ole A., Adan, Roger A. H., Ando, Tetsuya, Aschauer, Harald, Baker, Jessica H., Bencko, Vladimir, Bergen, Andrew W., Birgegård, Andreas, Boden, Joseph M., Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Brandt, Harry, Buehren, Katharina, Bulik, Cynthia M., Burghardt, Roland, Carlberg, Laura, Cassina, Matteo, Clementi, Maurizio, Cone, Roger D., Courtet, Philippe, Crawford, Steven, Crow, Scott, Crowley, James J., Danner, Unna N., Davis, Oliver S. P., de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E., Dick, Danielle M., Dina, Christian, Dmitrzak-Weglarz, Monika, Martinez, Elisa Docampo, Duncan, Laramie E., Egberts, Karin, Marshall, Christian R., Mattingsdal, Morten, McDevitt, Sara, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, James, Mitchell, Karen, Monteleone, Palmiero, Monteleone, Alessio Maria, Munn-Chernoff, Melissa A., Nacmias, Benedetta, Navratilova, Marie, Ntalla, Ioanna, Olsen, Catherine M., O'Toole, Julie K., Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Parker, Richard, Pearson, John F., Ehrlich, Stefan, Escaramís, Geòrgia, Espeseth, Thomas, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M., Fischer, Krista, Floyd, James A. B., Föcker, Manuel, Foretova, Lenka, Forzan, Monica, Franklin, Christopher S., Gallinger, Steven, Gambaro, Giovanni, Giegling, Ina, Giuranna, Johanna, Giusti-Rodríquez, Paola, Gonidakis, Fragiskos, Gordon, Scott, Gorwood, Philip, Mayora, Monica Gratacos, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine A., Hanscombe, Ken B., Hatzikotoulas, Konstantinos, Hebebrand, Johannes, Helder, Sietske G., Henders, Anjali K., Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Hinney, Anke, Horwood, L. John, Hübel, Christopher, Petersen, Liselotte V., Pinto, Dalila, Purves, Kirstin L., Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen W., Schmidt, Ulrike, Schork, Nicholas J., Schosser, Alexandra, Seitz, Jochen, Slachtova, Lenka, Slagboom, P. Eline, Slof-Op 't Landt, Margarita C. T., Slopien, Agnieszka, Soranzo, Nicole, Sorbi, Sandro, Southam, Lorraine, Steen, Vidar W., Strober, Michael, Huckins, Laura M., Hudson, James I., Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Johnson, Craig, Jordan, Jennifer, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Kaplan, Allan S., Kaprio, Jaakko, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J. H., Kaye, Walter H., Kennedy, Martin A., Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Kirk, Katherine M., Klareskog, Lars, Klump, Kelly L., Knudsen, Gun Peggy S., Larsen, Janne T., Le Hellard, Stephanie, Leppä, Virpi M., Li, Dong, Lichtenstein, Paul, Lilenfeld, Lisa, Lin, Bochao Danae, Lundervold, Astri, Luykx, Jurjen, Magistretti, Pierre J., Maj, Mario, Mannik, Katrin, Marsal, Sara, Stuber, Garret D., Szatkiewicz, Jin P., Tachmazidou, Ioanna, Tenconi, Elena, Thornton, Laura M., Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie A., van Furth, Eric F., Wade, Tracey D., Wagner, Gudrun, Walton, Esther, Watson, Hunna J., Whiteman, David C., Wichmann, H. Erich, Widen, Elisabeth, Woodside, D. Blake, Yao, Shuyang, Yilmaz, Zeynep, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Jungkunz, Martin, Mullins, N., Kang, J., Campos, A. I., Coleman, J. R. I., Edwards, A. C., Galfalvy, H., Levey, D. F., Lori, A., Shabalin, A., Starnawska, A., Su, M. -H., Watson, H. J., Adams, M., Awasthi, S., Gandal, M., Hafferty, J. D., Hishimoto, A., Kim, M., Okazaki, S., Otsuka, I., Ripke, S., Ware, E. B., Bergen, A. W., Berrettini, W. H., Bohus, M., Brandt, H., Chang, X., Chen, W. J., Chen, H. -C., Crawford, S., Crow, S., Diblasi, E., Duriez, P., Fernandez-Aranda, F., Fichter, M. M., Gallinger, S., Glatt, S. J., Gorwood, P., Guo, Y., Hakonarson, H., Halmi, K. A., Hwu, H. -G., Jain, S., Jamain, S., Jimenez-Murcia, S., Johnson, C., Kaplan, A. S., Kaye, W. H., Keel, P. K., Kennedy, J. L., Klump, K. L., Li, D., Liao, S. -C., Lieb, K., Lilenfeld, L., Liu, C. -M., Magistretti, P. J., Marshall, C. R., Mitchell, J. E., Monson, E. T., Myers, R. M., Pinto, D., Powers, A., Ramoz, N., Roepke, S., Rozanov, V., Scherer, S. W., Schmahl, C., Sokolowski, M., Strober, M., Thornton, L. M., Treasure, J., Tsuang, M. T., Witt, S. H., Woodside, D. B., Yilmaz, Z., Zillich, L., Adolfsson, R., Agartz, I., Air, T. M., Alda, M., Alfredsson, L., Andreassen, O. A., Anjorin, A., Appadurai, V., Soler Artigas, M., Van der Auwera, S., Azevedo, M. H., Bass, N., Bau, C. H. D., Baune, B. T., Bellivier, F., Berger, K., Biernacka, J. M., Bigdeli, T. B., Binder, E. B., Boehnke, M., Boks, M. P., Bosch, R., Braff, D. L., Bryant, R., Budde, M., Byrne, E. M., Cahn, W., Casas, M., Castelao, E., Cervilla, J. A., Chaumette, B., Cichon, S., Corvin, A., Craddock, N., Craig, D., Degenhardt, F., Djurovic, S., Edenberg, H. J., Fanous, A. H., Foo, J. C., Forstner, A. J., Frye, M., Fullerton, J. M., Gatt, J. M., Gejman, P. V., Giegling, I., Grabe, H. J., Green, M. J., Grevet, E. H., Grigoroiu-Serbanescu, M., Gutierrez, B., Guzman-Parra, J., Hamilton, S. P., Hamshere, M. L., Hartmann, A., Hauser, J., Heilmann-Heimbach, S., Hoffmann, P., Ising, M., Jones, I., Jones, L. A., Jonsson, L., Kahn, R. S., Kelsoe, J. R., Kendler, K. S., Kloiber, S., Koenen, K. C., Kogevinas, M., Konte, B., Krebs, M. -O., Landen, M., Lawrence, J., Leboyer, M., Lee, P. H., Levinson, D. F., Liao, C., Lissowska, J., Lucae, S., Mayoral, F., Mcelroy, S. L., Mcgrath, P., Mcguffin, P., Mcquillin, A., Medland, S. E., Mehta, D., Melle, I., Milaneschi, Y., Mitchell, P. B., Molina, E., Morken, G., Mortensen, P. B., Muller-Myhsok, B., Nievergelt, C., Nimgaonkar, V., Nothen, M. M., O'Donovan, M. C., Ophoff, R. A., Owen, M. J., Pato, C., Pato, M. T., Penninx, B. W. J. H., Pimm, J., Pistis, G., Potash, J. B., Power, R. A., Preisig, M., Quested, D., Ramos-Quiroga, J. A., Reif, A., Ribases, M., Richarte, V., Rietschel, M., Rivera, M., Roberts, A., Roberts, G., Rouleau, G. A., Rovaris, D. L., Rujescu, D., Sanchez-Mora, C., Sanders, A. R., Schofield, P. R., Schulze, T. G., Scott, L. J., Serretti, A., Shi, J., Shyn, S. I., Sirignano, L., Sklar, P., Smeland, O. B., Smoller, J. W., Sonuga-Barke, E. J. S., Spalletta, G., Strauss, J. S., Swiatkowska, B., Trzaskowski, M., Turecki, G., Vilar-Ribo, L., Vincent, J. B., Volzke, H., Walters, J. T. R., Shannon Weickert, C., Weickert, T. W., Weissman, M. M., Williams, L. M., Wray, N. R., Zai, C. C., Ashley-Koch, A. E., Beckham, J. C., Hauser, E. R., Hauser, M. A., Kimbrel, N. A., Lindquist, J. H., Mcmahon, B., Oslin, D. W., Qin, X., Mattheisen, M., Abdellaoui, A., Adams, M. J., Agerbo, E., Andlauer, T. F. M., Bacanu, S. -A., Baekvad-Hansen, M., Beekman, A. T. F., Bryois, J., Buttenschon, H. N., Bybjerg-Grauholm, J., Cai, N., Christensen, J. H., Clarke, T. -K., Colodro-Conde, L., Couvy-Duchesne, B., Crawford, G. E., Davies, G., Derks, E. M., Direk, N., Dolan, C. V., Dunn, E. C., Eley, T. C., Escott-Price, V., Hassan Kiadeh, F. F., Finucane, H. K., Frank, J., Gaspar, H. A., Gill, M., Goes, F. S., Gordon, S. D., Weinsheimer, S. M., Wellmann, J., Willemsen, G., Wu, Y., Xi, H. S., Yang, J., Zhang, F., Arolt, V., Boomsma, D. I., Dannlowski, U., Depaulo, J. R., Domenici, E., Domschke, K., Esko, T., Grove, J., Hall, L. S., Hansen, C. S., Hansen, T. F., Herms, S., Hickie, I. B., Homuth, G., Horn, C., Hottenga, J. -J., Hougaard, D. M., Howard, D. M., Jansen, R., Jorgenson, E., Knowles, J. A., Kohane, I. S., Kraft, J., Kretzschmar, W. W., Kutalik, Z., Li, Y., Lind, P. A., Macintyre, D. J., Mackinnon, D. F., Maier, R. M., Maier, W., Marchini, J., Mbarek, H., Middeldorp, C. M., Mihailov, E., Milani, L., Mondimore, F. M., Montgomery, G. W., Mostafavi, S., Nauck, M., Ng, B., Nivard, M. G., Nyholt, D. R., O'Reilly, P. F., Oskarsson, H., Hayward, C., Heath, A. C., Lewis, G., Li, Q. S., Madden, P. A. F., Magnusson, P. K., Martin, N. G., Mcintosh, A. M., Metspalu, A., Mors, O., Nordentoft, M., Paciga, S. A., Pedersen, N. L., Painter, J. N., Pedersen, C. B., Pedersen, M. G., Peterson, R. E., Peyrot, W. J., Posthuma, D., Quiroz, J. A., Qvist, P., Rice, J. P., Riley, B. P., Mirza, S. S., Schoevers, R., Schulte, E. C., Shen, L., Sigurdsson, E., Sinnamon, G. C. B., Smit, J. H., Smith, D. J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K. E., Teismann, H., Teumer, A., Thompson, W., Thomson, P. A., Thorgeirsson, T. E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A. G., Umbricht, D., der Auwera, S. V., van Hemert, A. M., Viktorin, A., Visscher, P. M., Wang, Y., Webb, B. T., Perlis, R. H., Porteous, D. J., Schaefer, C., Stefansson, K., Tiemeier, H., Uher, R., Werge, T., Lewis, C. M., Breen, G., Borglum, A. D., Sullivan, P. F., O'Connell, K. S., Coombes, B., Qiao, Z., Als, T. D., Borte, S., Charney, A. W., Drange, O. K., Gandal, M. J., Hagenaars, S. P., Ikeda, M., Kamitaki, N., Krebs, K., Panagiotaropoulou, G., Schilder, B. M., Sloofman, L. G., Winsvold, B. S., Won, H. -H., Abramova, L., Adorjan, K., Al Eissa, M., Albani, D., Alliey-Rodriguez, N., Antilla, V., Antoniou, A., Baek, J. H., Bauer, M., Beins, E. C., Bergen, S. E., Birner, A., Boen, E., Brum, M., Brumpton, B. M., Brunkhorst-Kanaan, N., Byerley, W., Cairns, M., Cervantes, P., Cruceanu, C., Cuellar-Barboza, A., Cunningham, J., Curtis, D., Czerski, P. M., Dale, A. M., Dalkner, N., David, F. S., Dobbyn, A. L., Douzenis, A., Elvsashagen, T., Ferrier, I. N., Fiorentino, A., Foroud, T. M., Forty, L., Frei, O., Freimer, N. B., Frisen, L., Gade, K., Garnham, J., Gelernter, J., Gizer, I. R., Gordon-Smith, K., Greenwood, T. A., Ha, K., Haraldsson, M., Hautzinger, M., Heilbronner, U., Hellgren, D., Holmans, P. A., Huckins, L., Johnson, J. S., Kalman, J. L., Kamatani, Y., Kittel-Schneider, S., Koromina, M., Kranz, T. M., Kranzler, H. R., Kubo, M., Kupka, R., Kushner, S. A., Lavebratt, C., Leber, M., Lee, H. -J., Levy, S. E., Lewis, C., Lundberg, M., Magnusson, S. H., Maihofer, A., Malaspina, D., Maratou, E., Martinsson, L., Mcgregor, N. W., Mckay, J. D., Medeiros, H., Millischer, V., Moran, J. L., Morris, D. W., Muhleisen, T. W., O'Brien, N., O'Donovan, C., Olde Loohuis, L. M., Oruc, L., Papiol, S., Pardinas, A. F., Perry, A., Pfennig, A., Porichi, E., Raj, T., Rapaport, M. H., Regeer, E. J., Rivas, F., Roth, J., Roussos, P., Ruderfer, D. M., Senner, F., Sharp, S., Shilling, P. D., Slaney, C., Sobell, J. L., Artigas, M. S., Spijker, A. T., Stein, D. J., Terao, C., Toma, C., Tooney, P., Tsermpini, E. -E., Vawter, M. P., Vedder, H., Xi, S., Xu, W., Kay Yang, J. M., Young, A. H., Young, H., Zandi, P. P., Zhou, H., HUNT All-In, Psychiatry, Babadjanova, G., Backlund, L., Bengesser, S., Blackwood, D. H. R., Carr, V. J., Catts, S., Dikeos, D., Etain, B., Ferentinos, P., Gawlik, M., Gershon, E. S., Henskens, F., Hillert, J., Hong, K. S., Hultman, C. M., Hveem, K., Iwata, N., Jablensky, A. V., Kirov, G., Lochner, C., Loughland, C., Mathews, C. A., Mcmahon, F. J., Michie, P., Mowry, B., Neale, B. M., Nievergelt, C. M., Oedegaard, K. J., Olsson, T., Pantelis, C., Patrinos, G. P., Reininghaus, E. Z., Saito, T., Schall, U., Schalling, M., Scott, R. J., Weickert, C. S., Stordal, E., Vaaler, A. E., Vieta, E., Waldman, I. D., Zwart, J. -A., Nurnberger, J. I., Stahl, E. A., Di Florio, A., Adan, R. A. H., Ando, T., Aschauer, H., Baker, J. H., Bencko, V., Birgegard, A., Boden, J. M., Boehm, I., Boni, C., Perica, V. B., Buehren, K., Bulik, C. M., Burghardt, R., Carlberg, L., Cassina, M., Clementi, M., Cone, R. D., Courtet, P., Crowley, J. J., Danner, U. N., Davis, O. S. P., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J. E., Dick, D. M., Dina, C., Dmitrzak-Weglarz, M., Martinez, E. D., Duncan, L. E., Egberts, K., Mattingsdal, M., Mcdevitt, S., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Monteleone, P., Monteleone, A. M., Munn-Chernoff, M. A., Nacmias, B., Navratilova, M., Ntalla, I., Olsen, C. M., O'Toole, J. K., Padyukov, L., Palotie, A., Pantel, J., Papezova, H., Parker, R., Pearson, J. F., Ehrlich, S., Escaramis, G., Espeseth, T., Estivill, X., Farmer, A., Favaro, A., Fischer, K., Floyd, J. A. B., Focker, M., Foretova, L., Forzan, M., Franklin, C. S., Gambaro, G., Giuranna, J., Giusti-Rodriquez, P., Gonidakis, F., Gordon, S., Mayora, M. G., Guillaume, S., Hanscombe, K. B., Hatzikotoulas, K., Hebebrand, J., Helder, S. G., Henders, A. K., Herpertz-Dahlmann, B., Herzog, W., Hinney, A., Horwood, L. J., Hubel, C., Petersen, L. V., Purves, K. L., Raevuori, A., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ritschel, F., Roberts, M., Rybakowski, F., Santonastaso, P., Scherag, A., Schmidt, U., Schork, N. J., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op 't Landt, M. C. T., Slopien, A., Soranzo, N., Sorbi, S., Southam, L., Steen, V. W., Huckins, L. M., Hudson, J. I., Imgart, H., Inoko, H., Janout, V., Jordan, J., Julia, A., Kalsi, G., Kaminska, D., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M. J. H., Kennedy, M. A., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Kirk, K. M., Klareskog, L., Knudsen, G. P. S., Larsen, J. T., Le Hellard, S., Leppa, V. M., Lichtenstein, P., Lin, B. D., Lundervold, A., Luykx, J., Maj, M., Mannik, K., Marsal, S., Stuber, G. D., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wade, T. D., Wagner, G., Walton, E., Whiteman, D. C., Wichmann, H. E., Widen, E., Yao, S., Zeggini, E., Zerwas, S., Zipfel, S., Jungkunz, M., Dietl, L., Schwarze, C. E., Dahmen, N., Schott, B. H., Mobascher, A., Crivelli, S., Dennis, M. F., Harvey, P. D., Carter, B. W., Huffman, J. E., Jacobson, D., Madduri, R., Olsen, M. K., Pestian, J., Gaziano, J. M., Muralidhar, S., Ramoni, R., Beckham, J., Chang, K. -M., O'Donnell, C. J., Tsao, P. S., Breeling, J., Huang, G., Romero, J. P. C., Moser, J., Whitbourne, S. B., Brewer, J. V., Aslan, M., Connor, T., Argyres, D. P., Stephens, B., Brophy, M. T., Humphries, D. E., Selva, L. E., Do, N., Shayan, S., Cho, K., Pyarajan, S., Hauser, E., Sun, Y., Zhao, H., Wilson, P., Mcardle, R., Dellitalia, L., Mattocks, K., Harley, J., Zablocki, C. J., Whittle, J., Jacono, F., Gutierrez, S., Gibson, G., Hammer, K., Kaminsky, L., Villareal, G., Kinlay, S., Xu, J., Hamner, M., Mathew, R., Bhushan, S., Iruvanti, P., Godschalk, M., Ballas, Z., Ivins, D., Mastorides, S., Moorman, J., Gappy, S., Klein, J., Ratcliffe, N., Florez, H., Okusaga, O., Murdoch, M., Sriram, P., Yeh, S. S., Tandon, N., Jhala, D., Aguayo, S., Cohen, D., Sharma, S., Liangpunsakul, S., Oursler, K. A., Whooley, M., Ahuja, S., Constans, J., Meyer, P., Greco, J., Rauchman, M., Servatius, R., Gaddy, M., Wallbom, A., Morgan, T., Stapley, T., Sherman, S., Ross, G., Tsao, P., Strollo, P., Boyko, E., Meyer, L., Gupta, S., Huq, M., Fayad, J., Hung, A., Lichy, J., Hurley, R., Robey, B., Striker, R., Erlangsen, A., Kessler, R. C., Porteous, D., Ursano, R. J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards A.C., Galfalvy H., Levey D.F., Lori A., Shabalin A., Starnawska A., Su M.-H., Watson H.J., Adams M., Awasthi S., Gandal M., Hafferty J.D., Hishimoto A., Kim M., Okazaki S., Otsuka I., Ripke S., Ware E.B., Bergen A.W., Berrettini W.H., Bohus M., Brandt H., Chang X., Chen W.J., Chen H.-C., Crawford S., Crow S., DiBlasi E., Duriez P., Fernandez-Aranda F., Fichter M.M., Gallinger S., Glatt S.J., Gorwood P., Guo Y., Hakonarson H., Halmi K.A., Hwu H.-G., Jain S., Jamain S., Jimenez-Murcia S., Johnson C., Kaplan A.S., Kaye W.H., Keel P.K., Kennedy J.L., Klump K.L., Li D., Liao S.-C., Lieb K., Lilenfeld L., Liu C.-M., Magistretti P.J., Marshall C.R., Mitchell J.E., Monson E.T., Myers R.M., Pinto D., Powers A., Ramoz N., Roepke S., Rozanov V., Scherer S.W., Schmahl C., Sokolowski M., Strober M., Thornton L.M., Treasure J., Tsuang M.T., Witt S.H., Woodside D.B., Yilmaz Z., Zillich L., Adolfsson R., Agartz I., Air T.M., Alda M., Alfredsson L., Andreassen O.A., Anjorin A., Appadurai V., Soler Artigas M., Van der Auwera S., Azevedo M.H., Bass N., Bau C.H.D., Baune B.T., Bellivier F., Berger K., Biernacka J.M., Bigdeli T.B., Binder E.B., Boehnke M., Boks M.P., Bosch R., Braff D.L., Bryant R., Budde M., Byrne E.M., Cahn W., Casas M., Castelao E., Cervilla J.A., Chaumette B., Cichon S., Corvin A., Craddock N., Craig D., Degenhardt F., Djurovic S., Edenberg H.J., Fanous A.H., Foo J.C., Forstner A.J., Frye M., Fullerton J.M., Gatt J.M., Gejman P.V., Giegling I., Grabe H.J., Green M.J., Grevet E.H., Grigoroiu-Serbanescu M., Gutierrez B., Guzman-Parra J., Hamilton S.P., Hamshere M.L., Hartmann A., Hauser J., Heilmann-Heimbach S., Hoffmann P., Ising M., Jones I., Jones L.A., Jonsson L., Kahn R.S., Kelsoe J.R., Kendler K.S., Kloiber S., Koenen K.C., Kogevinas M., Konte B., Krebs M.-O., Landen M., Lawrence J., Leboyer M., Lee P.H., Levinson D.F., Liao C., Lissowska J., Lucae S., Mayoral F., McElroy S.L., McGrath P., McGuffin P., McQuillin A., Medland S.E., Mehta D., Melle I., Milaneschi Y., Mitchell P.B., Molina E., Morken G., Mortensen P.B., Muller-Myhsok B., Nievergelt C., Nimgaonkar V., Nothen M.M., O'Donovan M.C., Ophoff R.A., Owen M.J., Pato C., Pato M.T., Penninx B.W.J.H., Pimm J., Pistis G., Potash J.B., Power R.A., Preisig M., Quested D., Ramos-Quiroga J.A., Reif A., Ribases M., Richarte V., Rietschel M., Rivera M., Roberts A., Roberts G., Rouleau G.A., Rovaris D.L., Rujescu D., Sanchez-Mora C., Sanders A.R., Schofield P.R., Schulze T.G., Scott L.J., Serretti A., Shi J., Shyn S.I., Sirignano L., Sklar P., Smeland O.B., Smoller J.W., Sonuga-Barke E.J.S., Spalletta G., Strauss J.S., Swiatkowska B., Trzaskowski M., Turecki G., Vilar-Ribo L., Vincent J.B., Volzke H., Walters J.T.R., Shannon Weickert C., Weickert T.W., Weissman M.M., Williams L.M., Wray N.R., Zai C.C., Ashley-Koch A.E., Beckham J.C., Hauser E.R., Hauser M.A., Kimbrel N.A., Lindquist J.H., McMahon B., Oslin D.W., Qin X., Mattheisen M., Abdellaoui A., Adams M.J., Agerbo E., Andlauer T.F.M., Bacanu S.-A., Baekvad-Hansen M., Beekman A.T.F., Bryois J., Buttenschon H.N., Bybjerg-Grauholm J., Cai N., Christensen J.H., Clarke T.-K., Colodro-Conde L., Couvy-Duchesne B., Crawford G.E., Davies G., Derks E.M., Direk N., Dolan C.V., Dunn E.C., Eley T.C., Escott-Price V., Hassan Kiadeh F.F., Finucane H.K., Frank J., Gaspar H.A., Gill M., Goes F.S., Gordon S.D., Weinsheimer S.M., Wellmann J., Willemsen G., Wu Y., Xi H.S., Yang J., Zhang F., Arolt V., Boomsma D.I., Dannlowski U., de Geus E.J.C., Depaulo J.R., Domenici E., Domschke K., Esko T., Grove J., Hall L.S., Hansen C.S., Hansen T.F., Herms S., Hickie I.B., Homuth G., Horn C., Hottenga J.-J., Hougaard D.M., Howard D.M., Jansen R., Jorgenson E., Knowles J.A., Kohane I.S., Kraft J., Kretzschmar W.W., Kutalik Z., Li Y., Lind P.A., MacIntyre D.J., MacKinnon D.F., Maier R.M., Maier W., Marchini J., Mbarek H., Middeldorp C.M., Mihailov E., Milani L., Mondimore F.M., Montgomery G.W., Mostafavi S., Nauck M., Ng B., Nivard M.G., Nyholt D.R., O'Reilly P.F., Oskarsson H., Hayward C., Heath A.C., Lewis G., Li Q.S., Madden P.A.F., Magnusson P.K., Martin N.G., McIntosh A.M., Metspalu A., Mors O., Nordentoft M., Paciga S.A., Pedersen N.L., Painter J.N., Pedersen C.B., Pedersen M.G., Peterson R.E., Peyrot W.J., Posthuma D., Quiroz J.A., Qvist P., Rice J.P., Riley B.P., Mirza S.S., Schoevers R., Schulte E.C., Shen L., Sigurdsson E., Sinnamon G.C.B., Smit J.H., Smith D.J., Stefansson H., Steinberg S., Streit F., Strohmaier J., Tansey K.E., Teismann H., Teumer A., Thompson W., Thomson P.A., Thorgeirsson T.E., Traylor M., Treutlein J., Trubetskoy V., Uitterlinden A.G., Umbricht D., der Auwera S.V., van Hemert A.M., Viktorin A., Visscher P.M., Wang Y., Webb B.T., Perlis R.H., Porteous D.J., Schaefer C., Stefansson K., Tiemeier H., Uher R., Werge T., Lewis C.M., Breen G., Borglum A.D., Sullivan P.F., O'Connell K.S., Coombes B., Qiao Z., Als T.D., Borte S., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Al Eissa M., Albani D., Alliey-Rodriguez N., Antilla V., Antoniou A., Baek J.H., Bauer M., Beins E.C., Bergen S.E., Birner A., Boen E., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Byerley W., Cairns M., Cervantes P., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Dobbyn A.L., Douzenis A., Elvsashagen T., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Gizer I.R., Gordon-Smith K., Greenwood T.A., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Holmans P.A., Huckins L., Johnson J.S., Kalman J.L., Kamatani Y., Kittel-Schneider S., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Leber M., Lee H.-J., Levy S.E., Lewis C., Lundberg M., Magnusson S.H., Maihofer A., Malaspina D., Maratou E., Martinsson L., McGregor N.W., McKay J.D., Medeiros H., Millischer V., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Raj T., Rapaport M.H., Regeer E.J., Rivas F., Roth J., Roussos P., Ruderfer D.M., Senner F., Sharp S., Shilling P.D., Slaney C., Sobell J.L., Artigas M.S., Spijker A.T., Stein D.J., Terao C., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Xi S., Xu W., Kay Yang J.M., Young A.H., Young H., Zandi P.P., Zhou H., HUNT All-In Psychiatry, Babadjanova G., Backlund L., Bengesser S., Blackwood D.H.R., Carr V.J., Catts S., Dikeos D., Etain B., Ferentinos P., Gawlik M., Gershon E.S., Henskens F., Hillert J., Hong K.S., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Kirov G., Lochner C., Loughland C., Mathews C.A., McMahon F.J., Michie P., Mowry B., Neale B.M., Nievergelt C.M., Oedegaard K.J., Olsson T., Pantelis C., Patrinos G.P., Reininghaus E.Z., Saito T., Schall U., Schalling M., Scott R.J., Weickert C.S., Stordal E., Vaaler A.E., Vieta E., Waldman I.D., Zwart J.-A., Nurnberger J.I., Stahl E.A., Di Florio A., Adan R.A.H., Ando T., Aschauer H., Baker J.H., Bencko V., Birgegard A., Boden J.M., Boehm I., Boni C., Perica V.B., Buehren K., Bulik C.M., Burghardt R., Carlberg L., Cassina M., Clementi M., Cone R.D., Courtet P., Crowley J.J., Danner U.N., Davis O.S.P., de Zwaan M., Dedoussis G., Degortes D., DeSocio J.E., Dick D.M., Dina C., Dmitrzak-Weglarz M., Martinez E.D., Duncan L.E., Egberts K., Mattingsdal M., McDevitt S., Meulenbelt I., Micali N., Mitchell J., Mitchell K., Monteleone P., Monteleone A.M., Munn-Chernoff M.A., Nacmias B., Navratilova M., Ntalla I., Olsen C.M., O'Toole J.K., Padyukov L., Palotie A., Pantel J., Papezova H., Parker R., Pearson J.F., Ehrlich S., Escaramis G., Espeseth T., Estivill X., Farmer A., Favaro A., Fischer K., Floyd J.A.B., Focker M., Foretova L., Forzan M., Franklin C.S., Gambaro G., Giuranna J., Giusti-Rodriquez P., Gonidakis F., Gordon S., Mayora M.G., Guillaume S., Hanscombe K.B., Hatzikotoulas K., Hebebrand J., Helder S.G., Henders A.K., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L.J., Hubel C., Petersen L.V., Purves K.L., Raevuori A., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ritschel F., Roberts M., Rybakowski F., Santonastaso P., Scherag A., Schmidt U., Schork N.J., Schosser A., Seitz J., Slachtova L., Slagboom P.E., Slof-Op 't Landt M.C.T., Slopien A., Soranzo N., Sorbi S., Southam L., Steen V.W., Huckins L.M., Hudson J.I., Imgart H., Inoko H., Janout V., Jordan J., Julia A., Kalsi G., Kaminska D., Kaprio J., Karhunen L., Karwautz A., Kas M.J.H., Kennedy M.A., Keski-Rahkonen A., Kiezebrink K., Kim Y.-R., Kirk K.M., Klareskog L., Knudsen G.P.S., Larsen J.T., Le Hellard S., Leppa V.M., Lichtenstein P., Lin B.D., Lundervold A., Luykx J., Maj M., Mannik K., Marsal S., Stuber G.D., Szatkiewicz J.P., Tachmazidou I., Tenconi E., Tortorella A., Tozzi F., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Whiteman D.C., Wichmann H.E., Widen E., Yao S., Zeggini E., Zerwas S., Zipfel S., Jungkunz M., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Mobascher A., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.-M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero J.P.C., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R., Erlangsen A., Kessler R.C., Porteous D., Ursano R.J., Wasserman D., Coon H., Demontis D., Docherty A.R., Kuo P.-H., Mann J.J., Renteria M.E., Stein M.B., and Willour V.
Subjects: LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract: Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., 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., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551
Published: 2022

22. Identification of Novel, Replicable Genetic Risk Loci for Suicidal Thoughts and Behaviors Among US Military Veterans

Author: Nathan A, Kimbrel, Allison E, Ashley-Koch, Xue J, Qin, Jennifer H, Lindquist, Melanie E, Garrett, Michelle F, Dennis, Lauren P, Hair, Jennifer E, Huffman, Daniel A, Jacobson, Ravi K, Madduri, Jodie A, Trafton, Hilary, Coon, Anna R, Docherty, Niamh, Mullins, Douglas M, Ruderfer, Philip D, Harvey, Benjamin H, McMahon, David W, Oslin, Jean C, Beckham, Elizabeth R, Hauser, Michael A, Hauser, and Robert, Striker
Subjects: Psychiatry and Mental health
Abstract: ImportanceSuicide is a leading cause of death; however, the molecular genetic basis of suicidal thoughts and behaviors (SITB) remains unknown.ObjectiveTo identify novel, replicable genomic risk loci for SITB.Design, Setting, and ParticipantsThis genome-wide association study included 633 778 US military veterans with and without SITB, as identified through electronic health records. GWAS was performed separately by ancestry, controlling for sex, age, and genetic substructure. Cross-ancestry risk loci were identified through meta-analysis. Study enrollment began in 2011 and is ongoing. Data were analyzed from November 2021 to August 2022.Main Outcome and MeasuresSITB.ResultsA total of 633 778 US military veterans were included in the analysis (57 152 [9%] female; 121 118 [19.1%] African ancestry, 8285 [1.3%] Asian ancestry, 452 767 [71.4%] European ancestry, and 51 608 [8.1%] Hispanic ancestry), including 121 211 individuals with SITB (19.1%). Meta-analysis identified more than 200 GWS (P −8) cross-ancestry risk single-nucleotide variants for SITB concentrated in 7 regions on chromosomes 2, 6, 9, 11, 14, 16, and 18. Top single-nucleotide variants were largely intronic in nature; 5 were independently replicated in ISGC, including rs6557168 in ESR1, rs12808482 in DRD2, rs77641763 in EXD3, rs10671545 in DCC, and rs36006172 in TRAF3. Associations for FBXL19 and AC018880.2 were not replicated. Gene-based analyses implicated 24 additional GWS cross-ancestry risk genes, including FURIN, TSNARE1, and the NCAM1-TTC12-ANKK1-DRD2 gene cluster. Cross-ancestry enrichment analyses revealed significant enrichment for expression in brain and pituitary tissue, synapse and ubiquitination processes, amphetamine addiction, parathyroid hormone synthesis, axon guidance, and dopaminergic pathways. Seven other unique European ancestry–specific GWS loci were identified, 2 of which (POM121L2 and METTL15/LINC02758) were replicated. Two additional GWS ancestry-specific loci were identified within the African ancestry (PET112/GATB) and Hispanic ancestry (intergenic locus on chromosome 4) subsets, both of which were replicated. No GWS loci were identified within the Asian ancestry subset; however, significant enrichment was observed for axon guidance, cyclic adenosine monophosphate signaling, focal adhesion, glutamatergic synapse, and oxytocin signaling pathways across all ancestries. Within the European ancestry subset, genetic correlations (r > 0.75) were observed between the SITB phenotype and a suicide attempt-only phenotype, depression, and posttraumatic stress disorder. Additionally, polygenic risk score analyses revealed that the Million Veteran Program polygenic risk score had nominally significant main effects in 2 independent samples of veterans of European and African ancestry.Conclusions and RelevanceThe findings of this analysis may advance understanding of the molecular genetic basis of SITB and provide evidence for ESR1, DRD2, TRAF3, and DCC as cross-ancestry candidate risk genes. More work is needed to replicate these findings and to determine if and how these genes might impact clinical care.
Published: 2023

23. The GenomeAsia 100K Project enables genetic discoveries across Asia

Author: Manjari Deshmukh, Stephan C. Schuster, Jong Il Kim, Venkatesan Radha, Partha P. Majumder, Herawati Sudoyo, Somasekar Seshagiri, John C. Chambers, Kok-Gan Chan, R. Rand Allingham, Vladimir Kharkov, Arkasubhra Ghosh, Ravi Gupta, Changhoon Kim, Keith C. Cheng, Lukas Forer, Thiramsett Sattibabu, Qixin Bei, Jeremy Stinson, Murray P. Cox, J. Stephen Lansing, Joseph Guillory, Akshi Bassi, Purushothaman Natarajan, Vadim Stepanov, George Koki, Markus S. Schröder, Ramesh Menon, Santosh Gopi Krishna Gadde, Elena S. Gusareva, Nidhan K. Biswas, Analabha Basu, Christian Fuchsberger, Michael A. Hauser, Santiago-Turla, Sandhya Nair, Mahesh Pratapneni, Sivasankar Malaichamy, Sebastian Schoenherr, Jonathan S. Friedlaender, Seik-Soon Khor, Jeong-Sun Seo, Aakrosh Ratan, Vivek Gopalan, Jeffrey D. Wall, Madasamy Parani, Tatiana M. Karafet, Viswanathan Mohan, Rikky W. Purbojati, Steffen Durinck, Anjali Verma, Kushal Suryamohan, Vedam L. Ramprasad, Badrul Munir Md-Zain, Phalkek Sameer, Andrew S. Peterson, Jong-Yeon Shin, Hie Lim Kim, Eric Stawiski, Joyner T. George, Michael F. Hammer, Katsushi Tokunaga, Jiani Li, Khai C. Ang, Sam Santhosh, Jennifer Tom, Syed Qasim Mehdi, Belong Cho, Tushar Bhangale, Asian School of the Environment, Lee Kong Chian School of Medicine (LKCMedicine), and Complexity Institute
Subjects: Asia, Genotype, Population structure, Population, Datasets as Topic, Disease, Article, 03 medical and health sciences, 0302 clinical medicine, Asian People, Genetic variation, Humans, Medicine [Science], education, Alleles, 030304 developmental biology, Genetic association, 0303 health sciences, education.field_of_study, Multidisciplinary, Genome, Human, Geography, Evolutionary biology, Genetic Discoveries, 030217 neurology & neurosurgery, Imputation (genetics), Founder effect, Reference genome, Genome-Wide Association Study
Abstract: The underrepresentation of non-Europeans in human genetic studies so far has limited the diversity of individuals in genomic datasets and led to reduced medical relevance for a large proportion of the world’s population. Population-specific reference genome datasets as well as genome-wide association studies in diverse populations are needed to address this issue. Here we describe the pilot phase of the GenomeAsia 100K Project. This includes a whole-genome sequencing reference dataset from 1,739 individuals of 219 population groups and 64 countries across Asia. We catalogue genetic variation, population structure, disease associations and founder effects. We also explore the use of this dataset in imputation, to facilitate genetic studies in populations across Asia and worldwide., Using whole-genome sequencing data from 1,739 individuals, the GenomeAsia 100K Project catalogues genetic variation, population structure and disease associations to facilitate genetic studies in Asian populations and increase representation in genetics studies worldwide.
Published: 2019

24. Diversity in Polygenic Risk of Primary Open-Angle Glaucoma

Author: Jessica N. Cooke Bailey, Kaitlyn L. Funk, Lauren A. Cruz, Andrea R. Waksmunski, Tyler G. Kinzy, Janey L. Wiggs, and Michael A. Hauser
Subjects: Genetics, Genetics (clinical)
Abstract: Glaucoma is the leading cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG), the most common glaucoma subtype, is more prevalent and severe in individuals of African ancestry. Unfortunately, this ancestral group has been historically under-represented among genetic studies of POAG. Moreover, both genetic and polygenic risk scores (GRS, PRS) that are typically based on genetic data from European-descent populations are not transferable to individuals without a majority of European ancestry. Given the aspirations of leveraging genetic information for precision medicine, GRS and PRS demonstrate clinical potential but fall short, in part due to the lack of diversity in these studies. Prioritizing diversity in the discovery of risk variants will improve the performance and utility of GRS and PRS-derived risk estimation for disease stratification, which could bring about earlier POAG intervention and treatment for a disease that often goes undetected until significant damage has occurred.
Published: 2022

25. Identification of Estrogen Signaling in a Prioritization Study of Intraocular Pressure-Associated Genes

Author: Louis R. Pasquale, Michael A. Hauser, Kristin Perkumas, Sylvia B. Smith, Yutao Liu, Emily J. Parker, Janey L. Wiggs, Jingwen Cai, Hannah Youngblood, Hongfang Yu, W. Daniel Stamer, Kathryn E. Bollinger, and Jason Sun
Subjects: primary open-angle glaucoma, genetic structures, Angiogenesis, QH301-705.5, Swine, Cell, Estrogen receptor, Biology, Catalysis, Article, Cell Line, Inorganic Chemistry, Extracellular matrix, Aqueous Humor, Trabecular Meshwork, medicine, Animals, Humans, estrogen signaling, Physical and Theoretical Chemistry, Biology (General), Cell adhesion, Molecular Biology, Gene, QD1-999, Spectroscopy, Intraocular Pressure, aqueous humor outflow, Organic Chemistry, Estrogens, General Medicine, eye diseases, Computer Science Applications, Cell biology, Extracellular Matrix, Chemistry, medicine.anatomical_structure, Cattle, Trabecular meshwork, sense organs, Estrogen receptor alpha, Glaucoma, Open-Angle, Signal Transduction
Abstract: Elevated intraocular pressure (IOP) is the only modifiable risk factor for primary open-angle glaucoma (POAG). Herein we sought to prioritize a set of previously identified IOP-associated genes using novel and previously published datasets. We identified several genes for future study, including several involved in cytoskeletal/extracellular matrix reorganization, cell adhesion, angiogenesis, and TGF-β signaling. Our differential correlation analysis of IOP-associated genes identified 295 pairs of 201 genes with differential correlation. Pathway analysis identified β-estradiol as the top upstream regulator of these genes with ESR1 mediating 25 interactions. Several genes (i.e., EFEMP1, FOXC1, and SPTBN1) regulated by β-estradiol/ESR1 were highly expressed in non-glaucomatous human trabecular meshwork (TM) or Schlemm’s canal (SC) cells and specifically expressed in TM/SC cell clusters defined by single-cell RNA-sequencing. We confirmed ESR1 gene and protein expression in human TM cells and TM/SC tissue with quantitative real-time PCR and immunofluorescence, respectively. 17β-estradiol was identified in bovine, porcine, and human aqueous humor (AH) using ELISA. In conclusion, we have identified estrogen receptor signaling as a key modulator of several IOP-associated genes. The expression of ESR1 and these IOP-associated genes in TM/SC tissue and the presence of 17β-estradiol in AH supports a role for estrogen signaling in IOP regulation.
Published: 2021

26. A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci

Author: Nathan A, Kimbrel, Allison E, Ashley-Koch, Xue J, Qin, Jennifer H, Lindquist, Melanie E, Garrett, Michelle F, Dennis, Lauren P, Hair, Jennifer E, Huffman, Daniel A, Jacobson, Ravi K, Madduri, Jodie A, Trafton, Hilary, Coon, Anna R, Docherty, Jooeun, Kang, Niamh, Mullins, Douglas M, Ruderfer, Philip D, Harvey, Benjamin H, McMahon, David W, Oslin, Elizabeth R, Hauser, Michael A, Hauser, and Jean C, Beckham
Subjects: Black or African American, Genetic Loci, Humans, Genetic Predisposition to Disease, Suicide, Attempted, Polymorphism, Single Nucleotide, White People, Genome-Wide Association Study, Veterans
Abstract: To identify pan-ancestry and ancestry-specific loci associated with attempting suicide among veterans, we conducted a genome-wide association study (GWAS) of suicide attempts within a large, multi-ancestry cohort of U.S. veterans enrolled in the Million Veterans Program (MVP). Cases were defined as veterans with a documented history of suicide attempts in the electronic health record (EHR; N = 14,089) and controls were defined as veterans with no documented history of suicidal thoughts or behaviors in the EHR (N = 395,064). GWAS was performed separately in each ancestry group, controlling for sex, age and genetic substructure. Pan-ancestry risk loci were identified through meta-analysis and included two genome-wide significant loci on chromosomes 20 (p = 3.64 × 10
Published: 2021

27. Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry

Author: Carly J. van der Heide, Jessica N. Cooke Bailey, Susan Williams, Dan Milea, José Paulo Cabral de Vasconcellos, Sadiq M. Abdullahi, Douglas E. Gaasterland, Ifeoma N. Asimadu, Sayoko E. Moroi, Hasnaa Lamari, Sarah J. Garnai, Janey L. Wiggs, Donald L. Budenz, R. Rand Allingham, Julia E. Richards, Jonathan L. Haines, Jerome I. Rotter, Michael G. Anderson, Xiuqing Guo, Robert M. Feldman, Michael A. Hauser, Yii-Der Ida Chen, Hugo Freire Nunes, Leon W. Herndon, John F. Ervin, Stephen Akafo, Radha Ayyagari, Thomas J. Hoffmann, Rachel W. Kuchtey, Michèle Ramsay, Prisca Biangoup Nyamsi, Zheng Li, Eric Jorgenson, Kar Seng Sim, Ebenezer Obeng-Nyarkoh, William C. Bromley, Christopher A. Girkin, Robert N. Weinreb, Alberta A H J Thiadens, Serge Resnikoff, William E. Sponsel, Maggie C.Y. Ng, Christine M. Hulette, Donald W. Bowden, Saydou Bakayoko, Jeffrey M. Liebmann, Harvey Dubiner, Suhanya Okeke, Abba Hydara, Ruth J. F. Loos, Adeyinka O. Ashaye, Olusegun Olaniyi, Mahmoud B. Alhassan, Khaled K. Abu-Amero, Christopher J Hammond, Tin Aung, John H. Fingert, Robert P. Igo, Shih-Hsiu Wang, Rui Barroso Schimiti, Pratap Challa, Robert F. Mullins, Rodolfo A. Perez-Grossmann, Nouhoum Guirou, Margaret A. Pericak-Vance, Anthony Okeke, Pieter W.M. Bonnemaijer, Paulo Vinicius Svidnicki, Abdoulaye Napo, Louise R. Pasquale, Joyce Kabwe, Chiea Chuen Khor, Mônica Barbosa de Melo, Girish N. Nadkarni, CM Chuka-Okosa, Neil Risch, Nkiru Kizor-Akaraiwe, Miles J. Flamme-Wiese, Cornelia M. van Duijn, N J Uche, Joseph Msosa, Olusola Olawoye, Linda M. Zangwill, Mariana B. Oliveira, Caroline C W Klaver, Allison E. Ashley Koch, Vital Paulino Costa, Ngoy Janvier Kilangalanga, Trevor R. Carmichael, Xue Qin, Kent D. Taylor, Yutao Liu, Dianne A. Cruz, Epidemiology, and Ophthalmology
Subjects: Male, medicine.medical_specialty, Genotype, genetic structures, Open angle glaucoma, Population, Black People, Glaucoma, Genome-wide association study, Polymorphism, Single Nucleotide, 01 natural sciences, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, Risk Factors, Interquartile range, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, 0101 mathematics, education, Adaptor Proteins, Signal Transducing, Aged, Original Investigation, education.field_of_study, Amyloid beta-Peptides, business.industry, 010102 general mathematics, Case-control study, General Medicine, Odds ratio, Middle Aged, medicine.disease, Immunohistochemistry, eye diseases, Case-Control Studies, Female, Risk assessment, business, Glaucoma, Open-Angle, Genome-Wide Association Study
Abstract: Importance: Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders.Objectives: To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma.Design, Settings, and Participants: A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma.Exposures: Genetic variants associated with primary open-angle glaucoma.Main Outcomes and Measures: Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10−8 in the discovery stage and in the meta-analysis of combined discovery and validation data.Results: A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10−8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10−13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry.Conclusions and Relevance: In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies.
Published: 2019

28. The social construction of genomics and genetic analysis in ocular diseases in Ibadan, South-western Nigeria

Author: Olusola Olawoye, Kabiru K. Salami, Abolaji Azeez, Precious Adebola, Tarela Sarimiye, John Imaledo, Tony Realini, Michael A. Hauser, and Adeyinka Ashaye
Subjects: Multidisciplinary, Face, Humans, Nigeria, Genetic Testing, Genomics, Eye
Abstract: Genomics, an emerging field to improve public health practice, has potential benefits to understanding ocular diseases. This study explored the social construction of genomics in ocular diseases in the blind community in Ibadan, Nigeria, through two focus group discussions and twelve in-depth interview sessions conducted among people living with ocular disorders. The data were thematic and content-analysed. Although the participants had limited knowledge about ocular diseases, genomics, and their nexus, they maintained a positive attitude toward its potential benefits. This informed their willingness to participate in genomics testing for ocular diseases. The participants preferred saliva-based sample collection over blood-based, and expressed concern for the procedure and accrued benefits of genomics studies. Thus, public sensitisation about ocular diseases and client-centred genomics testing procedures should be engendered.
Published: 2021

29. Postpump Aortic Insufficiency Is Transient After Valve Replacement with a Novel Prosthesis

Author: Eric E. Roselli, Shiva Sale, Lars G. Svensson, Edward G. Soltesz, Raphaelle A. Chemtob, Michael W. Hauser, Per Wierup, Daniel Wyler, Lee Wallace, Douglas R. Johnston, and Anand Mehta
Subjects: Heart Valve Prosthesis Implantation, medicine.medical_specialty, business.industry, medicine.medical_treatment, Aortic Valve Insufficiency, Aortic Valve Stenosis, medicine.disease, Prosthesis Design, Prosthesis, Cardiac surgery, Surgery, Valve replacement, Aortic valve replacement, Aortic Valve, Heart Valve Prosthesis, medicine, Humans, Radiology, Nuclear Medicine and imaging, Transient (computer programming), Cardiology and Cardiovascular Medicine, business
Published: 2020

30. Genetic predictors of hippocampal subfield volume in PTSD cases and trauma-exposed controls

Author: Melanie E. Garrett, Nathan A. Kimbrel, Jennifer S. Stevens, Michelle F. Dennis, Christine E. Marx, Jean C. Beckham, Allison E. Ashley-Koch, Sanne J.H. van Rooij, Courtney C. Haswell, Adriana Lori, Rajendra A. Morey, Gregory McCarthy, Emily K Clarke, Michael A. Hauser, Negar Fani, and Va Mid-Atlantic Mirecc Workgroup
Subjects: 050103 clinical psychology, hippocampus, hipocampo, RC435-571, TEPT, Hippocampus, Hippocampal formation, 海马, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Functional neuroimaging, subcampos hipocampales, Medicine, 0501 psychology and cognitive sciences, genetics, • Gene by environment interactions of genetic loci with both PTSD and childhood trauma on hippocampal phenotypes, 海马亚区, structural MRI, Psychiatry, childhood trauma, Basic Research Article, trauma infantil, business.industry, 05 social sciences, Resonancia magnética estructural, PTSD, 童年期创伤, genética, 030227 psychiatry, hippocampal subfields, Posttraumatic stress, Brain region, 结构性核磁共振, business, Neuroscience, Research Article, 遗传学
Abstract: Behavioural, structural, and functional neuroimaging have implicated the hippocampus as a critical brain region in posttraumatic stress disorder (PTSD) pathogenesis. Recent work in a normative, primarily European, sample identified 15 unique genetic loci contributing to structural variability in six hippocampal subfield volumes. We explored the relevance of these loci in two samples (Mental Illness Research Education and Clinical Centre [MIRECC] and Grady; n = 290) of trauma-exposed individuals enriched for PTSD and of diverse ancestry. Four of the previous loci demonstrated nominal evidence of replication in the MIRECC dataset, primarily within non-Hispanic whites (NHW). One locus replicated in the Grady cohort, which was composed exclusively of non-Hispanic blacks (NHB). Our data supported genetic interactions with diagnosis of lifetime PTSD and genetic interactions with childhood trauma in the MIRECC sample, but not the Grady sample. Given the racial, diagnostic, and trauma-exposure differences with the original genome-wide association study (GWAS) report, we conducted a full GWAS in the MIRECC and Grady datasets. Interactions between genetic variants and lifetime PTSD or childhood trauma were interrogated for single nucleotide polymorphisms (SNPs) with evidence of main effects. Genetic associations surpassed false discovery rate (FDR)-correction within hippocampal subfields in fimbria, subiculum, cornu ammonis-1 (CA1), and hippocampal amygdala transition area (HATA). One association was replicated in the Grady cohort (rs12880795 in TUNAR with left (L)-HATA volume). The most significant association in the MIRECC dataset was between rs6906714 in LINC02571 and right (R)-fimbria volume (p = 5.99×10−8, q = 0.0056). Interestingly, the effect of rs6906714 on R-fimbria volume increased with exposure to childhood trauma (gene*environment [G*E] interaction p = 0.022). These preliminary results argue for G*E interactions between genetic loci with PTSD and childhood trauma on hippocampal phenotypes. Our results underscore the need for larger neuroimaging-genetic studies in PTSD, trauma, and ancestrally diverse populations.
Published: 2020

31. Self-heating characterization and its applications in technology development

Author: A. Gupta, P. Yee, O. H. Gonzalez, T. Nigam, M. Nour, P. Paliwoda, D. Ioannou, Michael J. Hauser, L. Jiang, Luigi Pantisano, S. Cimino, Fernando Guarin, B. Min, Maria Toledano-Luque, David A. Lee, A. Vayshenker, Stewart E. Rauch, and W. Liu
Subjects: 010302 applied physics, Materials science, 02 engineering and technology, 021001 nanoscience & nanotechnology, 01 natural sciences, Temperature measurement, Characterization (materials science), Reliability (semiconductor), Planar, Thermal conductivity, Logic gate, 0103 physical sciences, Electronic engineering, 0210 nano-technology, Projection (set theory), Hot-carrier injection
Abstract: This work presents various device self-heating temperature sensing techniques and discusses their application in device reliability projection. Details of sensor design, technology choice, layout and ambient temperature impact on measurement results are discussed. The sensors produce excellent results which were confirmed through TCAD thermal simulation. Self-heating was studied by varying the number of fins per active region and proximity of sensor to heater was investigated. While most data presented here is on FinFET technology the learning and measurement techniques are applicable to planar technologies. Front-end-of-line (FEOL) reliability mechanism, hot carrier injection (HCI) was studied to show that self-heating effects can impact measurement results and recommendations are given on how to mitigate them. Self-heating is also studied for logic circuits by utilizing ring oscillators with several densities and stage counts to show that self-heating is considerably lower compared to constant voltage stress conditions conducted on discrete structures.
Published: 2020

32. An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci

Author: Andrew Ratanatharathorn, Robert J. Ursano, Mark W. Miller, Jasmeet P. Hayes, Dewleen G. Baker, Murray B. Stein, Bertrand Russ Huber, Jean C. Beckham, Victoria B. Risbrough, Caroline M. Nievergelt, Marco P. Boks, Nathan A. Kimbrel, Bart P. F. Rutten, Gerald A. Grant, Melanie E. Garrett, Mark W. Logue, Xuejun Qin, Christine E. Marx, Mieke Verfaellie, Elbert Geuze, Regina E. McGlinchey, Alicia K. Smith, William P. Milberg, Ronald C. Kessler, Monica Uddin, Zhenwei Zhou, Christiaan H. Vinkers, Yuanchao Zheng, Nikolaos P. Daskalakis, Eric Vermetten, Annjanette Stone, Michael A. Hauser, Erika J. Wolf, Filomene G. Morrison, Adam X. Maihofer, Allison E. Ashley-Koch, Steven A. Schichman, Erin B. Ware, MUMC+: MA Psychiatrie (3), Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Anatomy and neurosciences, and APH - Mental Health
Subjects: 0301 basic medicine, Oncology, Male, Candidate gene, Cell Cycle Proteins, Epigenesis, Genetic, Stress Disorders, Post-Traumatic, 0302 clinical medicine, Basic Helix-Loop-Helix Transcription Factors, Genetics (clinical), Oligonucleotide Array Sequence Analysis, Veterans, METABOLIC SYNDROME, PTSD, 3. Good health, Frontal Lobe, DNA methylation, Cohort, Female, Sulfotransferases, SMOKING, EXPRESSION, medicine.medical_specialty, CORTEX, Locus (genetics), PERIPHERAL-BLOOD, CONTROLLED-TRIAL, 03 medical and health sciences, AGE, Internal medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, Epigenetics, EXPOSURE, Molecular Biology, business.industry, Research, dNaM, Epigenome, DNA Methylation, GENE, Human genetics, United States, Repressor Proteins, 030104 developmental biology, Case-Control Studies, business, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract: Background Previous studies using candidate gene and genome-wide approaches have identified epigenetic changes in DNA methylation (DNAm) associated with posttraumatic stress disorder (PTSD). Methods In this study, we performed an EWAS of PTSD in a cohort of Veterans (n = 378 lifetime PTSD cases and 135 controls) from the Translational Research Center for TBI and Stress Disorders (TRACTS) cohort assessed using the Illumina EPIC Methylation BeadChip which assesses DNAm at more than 850,000 sites throughout the genome. Our model included covariates for ancestry, cell heterogeneity, sex, age, and a smoking score based on DNAm at 39 smoking-associated CpGs. We also examined in EPIC-based DNAm data generated from pre-frontal cortex (PFC) tissue from the National PTSD Brain Bank (n = 72). Results The analysis of blood samples yielded one genome-wide significant association with PTSD at cg19534438 in the gene G0S2 (p = 1.19 × 10-7, padj = 0.048). This association was replicated in an independent PGC-PTSD-EWAS consortium meta-analysis of military cohorts (p = 0.0024). We also observed association with the smoking-related locus cg05575921 in AHRR despite inclusion of a methylation-based smoking score covariate (p = 9.16 × 10-6), which replicates a previously observed PGC-PTSD-EWAS association (Smith et al. 2019), and yields evidence consistent with a smoking-independent effect. The top 100 EWAS loci were then examined in the PFC data. One of the blood-based PTSD loci, cg04130728 in CHST11, which was in the top 10 loci in blood, but which was not genome-wide significant, was significantly associated with PTSD in brain tissue (in blood p = 1.19 × 10-5, padj = 0.60, in brain, p = 0.00032 with the same direction of effect). Gene set enrichment analysis of the top 500 EWAS loci yielded several significant overlapping GO terms involved in pathogen response, including “Response to lipopolysaccharide” (p = 6.97 × 10-6, padj = 0.042). Conclusions The cross replication observed in independent cohorts is evidence that DNA methylation in peripheral tissue can yield consistent and replicable PTSD associations, and our results also suggest that that some PTSD associations observed in peripheral tissue may mirror associations in the brain.
Published: 2020

33. Identification and activity of the functional complex between hnRNPL and the pseudoexfoliation syndrome-associated lncRNA, LOXL1-AS1

Author: Nikolai P. Skiba, Michael A. Hauser, R. Rand Allingham, W. Daniel Stamer, Laura K. Finnegan, Inas F. Aboobakar, Maria Gomez-Caraballo, Heather Schmitt, William M. Johnson, David L. Corcoran, Megan Parker, and Shelby Strickland
Subjects: 0301 basic medicine, Pseudoexfoliation syndrome, Biology, Exfoliation Syndrome, Polymorphism, Single Nucleotide, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Gene expression, Genetics, medicine, Humans, Genetic Predisposition to Disease, Promoter Regions, Genetic, Molecular Biology, Genetics (clinical), Ribonucleoprotein, Messenger RNA, Pseudoexfoliation, RNA, General Medicine, medicine.disease, eye diseases, Cell biology, Cell nucleus, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, Ribonucleoproteins, 030220 oncology & carcinogenesis, Multiprotein Complexes, RNA, Long Noncoding, General Article, Amino Acid Oxidoreductases, Glaucoma, Open-Angle
Abstract: Individuals with pseudoexfoliation (PEX) syndrome exhibit various connective tissue pathologies associated with dysregulated extracellular matrix homeostasis. PEX glaucoma is a common, aggressive form of open-angle glaucoma resulting from the deposition of fibrillary material in the conventional outflow pathway. However, the molecular mechanisms that drive pathogenesis and genetic risk remain poorly understood. PEX glaucoma-associated single-nucleotide polymorphisms are located in and affect activity of the promoter of LOXL1-AS1, a long non-coding RNA (lncRNA). Nuclear and non-nuclear lncRNAs regulate a host of biological processes, and when dysregulated, contribute to disease. Here we report that LOXL1-AS1 localizes to the nucleus where it selectively binds to the mRNA processing protein, heterogeneous nuclear ribonucleoprotein-L (hnRNPL). Both components of this complex are critical for the regulation of global gene expression in ocular cells, making LOXL1-AS1 a prime target for investigation in PEX syndrome and glaucoma.
Published: 2020

34. Current progress and future direction in the genetics of PTSD: Focus on the development and contributions of the PGC-PTSD working group

Author: Jonathan Sebat, Jennifer A. Sumner, Alicia K. Smith, Caroline M. Nievergelt, Angela G. Junglen, Nicole R. Nugent, Adriana Lori, Christina M. Sheerin, Monica Uddin, Douglas L. Delahanty, Rajendra A. Morey, Michael A. Hauser, and Ananda B. Amstadter
Subjects: Posttraumatic stress, Genetic etiology, Genomics, Psychology, Working group, Genetic architecture, Clinical psychology
Abstract: An increasing body of research has focused on elucidating the genetic etiology of posttraumatic stress disorder (PTSD). This chapter first reviews the developments and existing knowledge in the rapidly growing field of PTSD genomics. Next, we describe the PTSD working group of the Psychiatric Genomics Consortium (PGC-PTSD), which was created to identify the genetic architecture underlying susceptibility to PTSD. We discuss recent developments underway by the PGC-PTSD working group, as well as address some of the unique considerations when investigating the genomics of PTSD. Five separate working groups within the PGC-PTSD are described with respect to their contributions to the overarching goal of answering innovative questions regarding the genetic and biological framework of PTSD. Finally, future directions of the overall PGC-PTSD working group, and the field of PTSD genomics as a whole, are discussed.
Published: 2020

35. Traumatic stress and accelerated DNA methylation age

Author: Sandro Galea, Kerry J. Ressler, Christiaan H. Vinkers, Elbert Geuze, Nathan A. Kimbrel, Caroline M. Nievergelt, Michael A. Hauser, Don Armstrong, Erika J. Wolf, Jean C. Beckham, Ronald C. Kessler, Hannah Maniates, Eric Vermetten, Andrew Ratanatharathorn, Victoria B. Risbrough, Marco P. Boks, Alicia K. Smith, Karestan C. Koenen, Adam X. Maihofer, Robert J. Ursano, Mark W. Miller, Bart P. F. Rutten, Melanie E. Garrett, Dewleen G. Baker, Allison E. Aiello, Murray B. Stein, Adriana Lori, Allison E. Ashley-Koch, Va Mid-Atlantic Mirecc Workgroup, Mark W. Logue, Nicole R. Nugent, Monica Uddin, APH - Mental Health, RS: MHeNs - R3 - Neuroscience, and Psychiatrie & Neuropsychologie
Subjects: 0301 basic medicine, Oncology, DISORDER, Male, Epigenetic clock, Endocrinology, Diabetes and Metabolism, INVENTORY, Genome-wide association study, EPIGENETIC CLOCK ANALYSIS, Epigenesis, Genetic, Cohort Studies, Stress Disorders, Post-Traumatic, 0302 clinical medicine, Endocrinology, Stress Disorders, Post-Traumatic/genetics, Stress Disorders, Trauma Severity Indices, DNA methylation, Traumatic stress, PTSD, Middle Aged, Psychiatry and Mental health, Meta-analysis, Female, MENTAL-HEALTH, Accelerated aging, Cohort study, Adult, medicine.medical_specialty, Genomics, Article, 03 medical and health sciences, Genetic, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Epigenetics, GENOME-WIDE ASSOCIATION, PATIENT DATA, Biological Psychiatry, Endocrine and Autonomic Systems, business.industry, RESILIENCE, Additional research, 030104 developmental biology, PSYCHOMETRIC PROPERTIES, Post-Traumatic/genetics, INTERNATIONAL DIAGNOSTIC INTERVIEW, TELOMERE LENGTH, business, INDIVIDUAL PARTICIPANT DATA, CORTICAL THICKNESS, 030217 neurology & neurosurgery, Epigenesis
Abstract: Background: Recent studies examining the association between posttraumatic stress disorder (PTSD) and accelerated aging, as defined by DNA methylation-based estimates of cellular age that exceed chronological age, have yielded mixed results. Methods: We conducted a meta-analysis of trauma exposure and PTSD diagnosis and symptom severity in association with accelerated DNA methylation age using data from 9 cohorts contributing to the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (combined N = 2186). Associations between demographic and cellular variables and accelerated DNA methylation age were also examined, as was the moderating influence of demographic variables. Results: Meta-analysis of regression coefficients from contributing cohorts revealed that childhood trauma exposure (when measured with the Childhood Trauma Questionnaire) and lifetime PTSD severity evidenced significant, albeit small, meta-analytic associations with accelerated DNA methylation age (ps = 0.028 and 0.016, respectively). Sex, CD4T cell proportions, and natural killer cell proportions were also significantly associated with accelerated DNA methylation age (all ps < 0.02). PTSD diagnosis and lifetime trauma exposure were not associated with advanced DNA methylation age. There was no evidence of moderation of the trauma or PTSD variables by demographic factors. Conclusions: Results suggest that traumatic stress is associated with advanced epigenetic age and raise the possibility that cells integral to immune system maintenance and responsivity play a role in this. This study highlights the need for additional research into the biological mechanisms linking traumatic stress to accelerated DNA methylation age and the importance of furthering our understanding of the neurobiological and health consequences of PTSD. © 2017
Published: 2018

36. Transcriptome analysis of adult and fetal trabecular meshwork, cornea, and ciliary body tissues by RNA sequencing

Author: Michael A. Hauser, Megan U. Carnes, R. Rand Allingham, and Allison E. Ashley-Koch
Subjects: Male, 0301 basic medicine, Candidate gene, Pathology, medicine.medical_specialty, genetic structures, Glaucoma, Gestational Age, Biology, Cornea, Transcriptome, Tonometry, Ocular, 03 medical and health sciences, Cellular and Molecular Neuroscience, Fetus, 0302 clinical medicine, Ciliary body, Trabecular Meshwork, Gene expression, medicine, Humans, Eye Proteins, Gene, Intraocular Pressure, Aged, Sequence Analysis, RNA, Gene Expression Profiling, Ciliary Body, Gene Expression Regulation, Developmental, medicine.disease, eye diseases, Sensory Systems, Ophthalmology, 030104 developmental biology, medicine.anatomical_structure, 030221 ophthalmology & optometry, Female, sense organs, Trabecular meshwork, Glaucoma, Open-Angle
Abstract: Purpose To characterize the transcriptional landscape of human adult and fetal trabecular meshwork (TM), cornea, and ciliary body (CB) tissues, and to evaluate the expression level of candidate genes selected from genetic association studies of primary-open angle glaucoma, central corneal thickness, intraocular pressure, vertical cup to disc ratio, and optic nerve parameters. Methods Deep RNA sequencing was performed on the selected human tissues. Transcriptome analyses were performed to 1) characterize the total number of expressed genes, 2) identify the most highly expressed genes, 3) estimate the number of novel transcripts, and 4) evaluate the expression of candidate genes in each tissue. Finally, a differential gene expression analysis was conducted to compare the adult and fetal ocular tissues. Results There was an average of 12,362 protein coding genes and 3725 novel transcripts expressed in each tissue. The top most expressed genes in each tissue included SPARC (fetal cornea and TM), APOD (adult TM), CLU (adult cornea), and PTGDS (adult and fetal CB). Twenty-nine candidate genes selected from genetic association studies primarily showed high expression levels in the trabecular meshwork and cornea. Comparison of adult and fetal samples identified 2012 and 1261 differentially expressed protein-coding genes within the cornea and trabecular meshwork, respectively. Conclusions This study has provided an unbiased glimpse into the transcriptome of three essential anterior ocular tissues, resulting in the development of several novel hypotheses. These data can be used in the future to better guide ocular research questions.
Published: 2018

37. Association of Smoking, Alcohol Consumption, Blood Pressure, Body Mass Index, and Glycemic Risk Factors With Age-Related Macular Degeneration

Author: Itay Chowers, Stacy M Meuer, R. Theodore Smith, Bamini Gopinath, Brendan J Vote, Thierry Léveillard, David A Mackey, Dwight Stambolian, Jamie E Craig, José-Alain Sahel, David J Hunter, Michael L Klein, Jane Romm, Robyn H Guymer, Mingyao Li, J. L. Haines, Emily L. Moore, J Allie McGrath, Chloe M. Stanton, Danni Lin, Jessica N Cooke Bailey, Anton Orlin, Anita Agarwal, Frank G Holz, Debra A Schaumberg, Valerie Kuan, Christine A. Curcio, Ken Flagg, Sudha K Iyengar, Sebanti Sengupta, Bal Dhillon, Joanna E. Merriam, Janette Hall, Bernhard H F Weber, Caroline Brandl, Donald Zack, Eric Souied, Yara T. E. Lechanteur, Christina A Rennie, Mathias Gorski, Murray H Brilliant, Denise J. Morgan, Barbara Truitt, Daniel E Weeks, Thomas Langmann, Aroon D. Hingorani, Gerald Liew, Andrea J Richardson, Neal S Peachey, John Blangero, Alasdair Warwick, Humma Shahid, Eiko K de Jong, Kari E Branham, S. V. Goverdhan, Paul Mitchell, Angela J Cree, Margaux A. Morrison, Rebecca J Sardell, Ian J Constable, Michael A. Hauser, Zhenglin Yang, Reneé Laux, G. Rudolph, David Cho, Jie Jin Wang, Albert Caramoy, Jaclyn L Kovach, Alexander Brucker, Frédéric Blond, Hongrong Luo, Michael B Gorin, Robert P Igo, Caroline C W Klaver, Lebriz Ersoy, Timothy Isaacs, Adnan Tufail, Gabriëlle H.S. Buitendijk, Nicholas Katsanis, Stephen Burgess, Carel B Hoyng, Reecha Sofat, Ivana K Kim, Mohammad Othman, Ian L McAllister, Giuliana Silvestri, Helena Hai Liang, Margaret DeAngelis, Matthew P Johnson, Ava G Tan, Felix Grassmann, Lindsay A Farrer, Alex W Hewitt, Hong Ouyang, Cindy Wen, Henry Ferreyra, Milam A Brantley, Melinda Cain, Caroline Hayward, Kristine E. Lee, Linn Gieser, Isabelle Audo, Evangelia E Tsironi, Nicole T.M. Saksens, Hendrik P N Scholl, Stephen G Schwartz, Matthias Olden, Saddek Mohand-Said, Scott J Hebbring, Joshua D Hoffman, Shira Hagbi-Levi, Anthony T Moore, Mustapha Benchaboune, Lars G Fritsche, Margaret A Pericak-Vance, Iris M Heid, Kyu Hyung Park, Jennifer L Bragg-Gresham, Hélène Blanché, Alexis Boleda, Rando Allikmets, John R Heckenlively, Kathryn P Burdon, Elisa Bala, Rinki Ratnapriya, Kimberly F Doheny, Xiaowei Zhan, Sascha Fauser, Claudia N von Strachwitz, Ronald Klein, Johanna R. Foerster, Wilmar Igl, Andrew J Lotery, Klaus Stark, Matthew Brooks, Jane C Khan, Emily Y Chew, Paul N Baird, Cornelia M Van Duijn, Chelsea E. Myers, Anneke I den Hollander, Monique D Courtenay, Zhiguang Su, Yingda Jiang, William K Scott, Tammy M Martin, Armin Wolf, Jeeyun Ahn, John C. Merriam, Eric A Postel, Guanping Mao, Emmanuelle Souzeau, Barbara E K Klein, Terrie Kitchner, Stewart Lake, Anand Swaroop, Valentina Cipriani, Tina Schick, Stephanie A. Hagstrom, Alan M. Kwong, Daniel Chen, Gonçalo R. Abecasis, Matthew Schu, Michelle Grunin, John R.W. Yates, Peter Campochiaro, Kang Zhang, and Jean-François Deleuze
Subjects: Vascular Endothelial Growth Factor A, medicine.medical_specialty, Alcohol Drinking, medicine.medical_treatment, Visual Acuity, Angiogenesis Inhibitors, Blood Pressure, Type 2 diabetes, Blindness, Lower risk, Body Mass Index, Risk Factors, Internal medicine, Mendelian randomization, Humans, Medicine, Risk factor, Glycemic, business.industry, Smoking, Odds ratio, Mendelian Randomization Analysis, medicine.disease, Ophthalmology, Diabetes Mellitus, Type 2, Wet Macular Degeneration, Smoking cessation, business, Body mass index, Genome-Wide Association Study
Abstract: Importance Advanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD. Objective To assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD. Design, Setting, Participants This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P
Published: 2021

38. Modeling Glaucoma: Retinal Ganglion Cells Generated from Induced Pluripotent Stem Cells of Patients with SIX6 Risk Allele Show Developmental Abnormalities

Author: Pooja Teotia, R. Rand Allingham, Christopher S. Wichman, Michael A. Hauser, Matthew J. Van Hook, and Iqbal Ahmad
Subjects: Male, Retinal Ganglion Cells, 0301 basic medicine, genetic structures, Neurite, Induced Pluripotent Stem Cells, Gene Expression, Glaucoma, Biology, Retinal ganglion, 03 medical and health sciences, CDKN2A, medicine, Humans, Induced pluripotent stem cell, Alleles, Homeodomain Proteins, Genetics, Cell Differentiation, Cell Biology, medicine.disease, eye diseases, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Retinal ganglion cell, Trans-Activators, Molecular Medicine, Female, sense organs, Signal transduction, Stem cell, Developmental Biology
Abstract: Glaucoma represents a group of multifactorial diseases with a unifying pathology of progressive retinal ganglion cell (RGC) degeneration, causing irreversible vision loss. To test the hypothesis that RGCs are intrinsically vulnerable in glaucoma, we have developed an in vitro model using the SIX6 risk allele carrying glaucoma patient-specific induced pluripotent stem cells (iPSCs) for generating functional RGCs. Here, we demonstrate that the efficiency of RGC generation by SIX6 risk allele iPSCs is significantly lower than iPSCs-derived from healthy, age- and sex-matched controls. The decrease in the number of RGC generation is accompanied by repressed developmental expression of RGC regulatory genes. The SIX6 risk allele RGCs display short and simple neurites, reduced expression of guidance molecules, and immature electrophysiological signature. In addition, these cells have higher expression of glaucoma-associated genes, CDKN2A and CDKN2B, suggesting an early onset of the disease phenotype. Consistent with the developmental abnormalities, the SIX6 risk allele RGCs display global dysregulation of genes which map on developmentally relevant biological processes for RGC differentiation and signaling pathways such as mammalian target of rapamycin that integrate diverse functions for differentiation, metabolism, and survival. The results suggest that SIX6 influences different stages of RGC differentiation and their survival; therefore, alteration in SIX6 function due to the risk allele may lead to cellular and molecular abnormalities. These abnormalities, if carried into adulthood, may make RGCs vulnerable in glaucoma.
Published: 2017

39. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci

Author: Daniele Cusi, Etsuo Chihara, Leyla Al-Jasim, Ya Xing Wang, Tero Kivelä, Jinghong Sang, Adeyinka O. Ashaye, Bowen Zhao, Tan Do, Susanne Moebus, Ursula Schlötzer-Schrehardt, Shamira A. Perera, Augustine W O Cheong, Afsaneh Naderi Beni, Francisco A. Escudero-Domínguez, Yoshiaki Kiuchi, Tomomi Higashide, DS Klobassa, Friedrich E. Kruse, Nicole Weisschuh, Chunyan Qiao, Muhammad Imran Khan, Martin L. Hibberd, Arthur J. Sit, Jamie E Craig, Akitoshi Yoshida, Periasamy Sundaresan, Humaira Ayub, Kathryn P. Burdon, Jonathan G Crowston, Kazunori Miyata, Marisa Cruz-Aguilar, Markus M. Nöthen, Hasnaa Lamari, Michael A. Hauser, Louis R. Pasquale, Anneke I. den Hollander, Eija Vesti, Ursula Hoja, Raphael Q Soh, Burcu Kasım, Adeola O Onakoya, Rachel W. Kuchtey, Eugeny L. Akopov, Liang Xu, Juan Carlos Zenteno, Chaiwat Teekhasaenee, Saleh A. Al-Obeidan, Eleftherios Anastasopoulos, Anita S Y Chan, Nagahisa Yoshimura, John Kuchtey, Naris Kitnarong, Yaan Fun Chong, Boonsong Wanichwecharugruang, R.R. Fayzrakhmanov, Paul Mitchell, N Kalpana, Unnur Thorsteinsdottir, Kei Tashiro, Rajesh Kumar, Jin Wook Jeoung, Deepak P. Edward, Frederico Martinon-Torres, Bilge Batu, Anavaj Sakuntabhai, Robert N. Weinreb, Héctor González-Iglesias, Sasan Moghimi, Jia Nee Foo, Nkechi J Uche, Karen Curtin, Kenji Inoue, Lingam Vijaya, Makoto Aihara, Dilek Aktas, Norimoto Gotoh, Wasu Supakontanasan, Laura Dallorto, Takako Sugimoto, Jonathan L. Haines, Olusola Olawoye, Janey L. Wiggs, Sripriya Sarangapani, Craig J. Chaya, Theofanis Pappas, Fotis Topouzis, Eranga N. Vithana, Steffen Heegaard, Fridbert Jonasson, Kazuhiko Mori, Idakwo Ugbede, Hongyan Jia, Anthi Chatzikyriakidou, Robert P. Igo, Soon Cheol Cha, Yueming Chen, Su-Ling Ho, Zhenglin Yang, Jost B. Jonas, Francesca Pasutto, Ken Hayashi, Rahat Husain, Georg Mossböck, S Fabian Lerner, R. Rand Allingham, Priti Sahay, Fumihiko Matsuda, Yanin Suwan, Teresa Rolle, Robert Ritch, Peter Kraft, Trevor R. Carmichael, Kar Seng Sim, Raheel Qamar, Gordana Sunaric Megevand, Tomasz Zarnowski, Shazia Micheal, Scott Thomas, Paolo Frezzotti, Vera Vysochinskaya, Linda M. Zangwill, Alina Popa Cherecheanu, Tin Aung, Jessica N. Cooke Bailey, Kyu Hyung Park, Edward Dervan, Suhanya Okeke, Pablo Fornero, Sidi M Ezzouhairi, Pascal Reynier, Gudmar Thorleifsson, Michael V. Dubina, Kazuhisa Sugiyama, Sylvain Roy, Per Kappelgaard, Mineo Ozaki, Vijayan Saravanan, Carlo Lavia, Wenda L. Greer, Takanori Mizoguchi, Alireza Lashay, A. Binder, Daniel Berner, Su Qin Peh, Balram Chowbay, Nino Kobakhidze, Ifeoma N. Asimadu, Delia Sivori, Gopalakrishnan Prakadeeswari, Alexandros Lambropoulos, Michael Coote, Sergei Y. Astakhov, Shahin Yazdani, Dan Milea, Montserrat García, Lydia Álvarez, Kenji Yamashiro, Soumya Raychaudhuri, Pratap Challa, Aparna Rao, Jae H. Kang, Khai Koon Heng, Richard K. Lee, Tien Yin Wong, Alex W. Hewitt, Yoko Ikeda, Kessara Pathanapitoon, Panayiota Founti, Daniella Bach-Holm, Emmanuelle Souzeau, Margaret A. Pericak-Vance, Michèle Ramsay, Nkiru Kizor-Akaraiwe, Yosai Mori, Antonio Maria Fea, Chandrashekaran Shivkumar, Xiao Yu Ng, Jie Jin Wang, Erika Salvi, Giang T T Nguyn, Steffen Uebe, Tamara Zompa, Anne L. Coleman, Werner Zenz, Min Sagong, Luis Fernández-Vega Cueto, Farah Akhtar, Susan Williams, Sarah C. Nelson, Bradford J. Shingleton, Ryuichi Ideta, Leon W. Herndon, Zheng Li, Murat Irkec, M. Roy Wilson, Ewa Kosior-Jarecka, Christian Y. Mardin, Mozhgan Rezaei Kanavi, Tsutomu Ohashi, Abderrahman Rafei, Rengaraj Venkatesh, Stefan Herms, George Chichua, Mohammad Pakravan, Robyn M. Rautenbach, Shi Qi Mok, Trình V Nguyn, Patricio G. Schlottmann, Nassim Khatibi, Daniel Gaston, Masaru Inatani, Morio Ueno, Mukharram M. Bikbov, Eoin Silke, Homa Naderifar, Linda Hansapinyo, Paolo Manunta, Z. Xie, Urszula Lukasik, Eray Atalay, Lulin Huang, Xuyang Liu, Chie Sotozono, Shuang Ru Goh, John H. Fingert, Richard A. Mills, Khaled K. Abu-Amero, Xiao Yin Chen, Matthias Zenkel, Sergo Tabagari, Irma Järvelä, Xueyi Chen, Stéphanie Leruez, Yury S. Astakhov, Sonia Davila, Yildirim Nilgün, Ronnie George, Shin-ichi Manabe, Miguel Coca-Prados, Masahiro Miyake, Ignacio Lischinsky, Rogelio González-Sarmiento, Arkasubhra Ghosh, A. Emelyanov, Çilingir Oguz, Masakazu Nakano, Rohit Shetty, Karen Bedard, Toshiya Sakurai, Yutao Liu, Barbara M Wirostko, Hui Zhang, Ulrich-Christoph Welge-Luessen, Toshiaki Kubota, Vania Castro, Hip X Nguyn, Liyun Jia, Ari Ziskind, Hideki Chuman, Andrew C. Orr, Satoko Nakano, Daniela Paoli, Masahide Yanagi, Aravind Haripriya, Kari Stefansson, Pedro Pablo Rodríguez-Calvo, Hui Meng Soo, Chiea Chuen Khor, Gyulli M. Kazakbaeva, Osvaldo Cuello, Mei Chin Lee, Ki Ho Park, Natalia Porporato, Lourdes de Juan Marcos, Ching-Yu Cheng, Shigeyasu Kazama, Shigeru Kinoshita, Axel M. Hillmer, Alan S. Crandall, Victor H. K. Yong, Ohoud Owaidhah, Rodolfo Perez Grossmann, Jeeyun Ahn, André Reis, Nevbahar Tamçelik, Satoshi Ishiko, Antonio Salas, Ningli Wang, Singapore Eye Research Institute [Singapore] (SERI), Ozaki Eye Hospital [Miyazaki], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), deCODE genetics [Reykjavik], Mizoguchi Eye Hospital [Sasebo], Case Western Reserve University [Cleveland], Aravind Eye Hospital [Madurai, India], University of the Witwatersrand [Johannesburg] (WITS), Pavlov First Saint Petersburg State Medical University [St. Petersburg], Dalhousie University [Halifax], Flinders University [Adelaide, Australia], Kyoto Prefectural University of Medicine [Kyoto, Japon], King Saud University [Riyadh] (KSU), Genome Institute of Singapore (GIS), Aravind Medical Research Foundation (AMRF), Université de Médecine Carol Davila, Harvard Medical School [Boston] (HMS), University of Washington [Seattle], Hayashi Eye Hospital [Fukuoka], Shinjo Eye Clinic [Nagoya], Medical University of Lublin, Inoue Eye Hospital [Tokyo], Hacettepe University = Hacettepe Üniversitesi, Universidad de Oviedo [Oviedo], Kanazawa University (KU), Department of Medical and Clinical Genetics [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Organizacion Medica de Investigacion (OMI BUENOS AIRES), Fundacion para el Estudio del Glaucoma [Buenos Aires], Chercheur indépendant, Eskisehir Osmangazi University, Ufa Eye Research Institute [Bashkortostan], Seoul National University Hospital, Yeungnam University [South Korea], Kyoto University, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Universität Heidelberg [Heidelberg] = Heidelberg University, Birla Institute of Scientific Research (BISR), B. M. Birla Science and Technology Center, Faculty of Computer Science, Department of Pathology and Immunology, Geneva University Hospital (HUG), Key Laboratory for Information System Security, ministry of education, Numerical modeling and high performance computing for evolution problems in complex domains and heterogeneous media (NACHOS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Alexandre Dieudonné (LJAD), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institute of Human Genetics [Erlangen, Allemagne], Department of Ophthalmology, School of Medicine [Thessaloniki, Grèce], Aristotle University of Thessaloniki, Università degli Studi di Siena = University of Siena (UNISI), Department of Medicine, Surgery, and Dentistry, University of Milano, Japan Advanced Institute of Science and Technology (JAIST), Etudes génomiques trans-ethniques des maladies multifactorielles, Kyoto University-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Archaeogenetics Laboratory, Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Rheinische Friedrich-Wilhelms-Universität Bonn, University of Kentucky (UK), Helsinki University Eye Hospital, Turku University Hospital, Turku, Finland, COMSATS Institute of Information Technology (CIIT), Department of Epidemiology, Harvard School of Public Health, University of Miami Leonard M. Miller School of Medicine (UMMSM), Brigham and Women's Hospital [Boston], Department of Neuroscience and Pharmacology, Section of Eye Pathology, University of Copenhagen, University of Copenhagen = Københavns Universitet (UCPH), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of California [San Diego] (UC San Diego), University of California (UC), University of Iceland [Reykjavik], New York Eye and Ear Infirmary of Mount Sinai [New York] (NYEE), Oita University Faculty of Medicine [Oita, Japon], Radboud University Medical Center [Nijmegen], Oogheelkunde, RS: FHML non-thematic output, Kyoto University [Kyoto], Universidad Nacional Autónoma de México (UNAM), Universität Heidelberg [Heidelberg], Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Alexandre Dieudonné (JAD), Dipartimento di Scienze oftalmologiche e Neurochirurgiche, Universita' degli Studi di Siena, Siena, Kyoto University [Kyoto]-Institut National de la Santé et de la Recherche Médicale (INSERM), Rothschild Hospital, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), University of Kentucky, University of Copenhagen = Københavns Universitet (KU), University of California, Aung, Tin, Ozaki, Mineo, Lee, Mei Chin, Schlötzer Schrehardt, Ursula, Thorleifsson, Gudmar, Mizoguchi, Takanori, Igo, Robert P, Haripriya, Aravind, Williams, Susan E, Astakhov, Yury S, Orr, Andrew C, Burdon, Kathryn P, Nakano, Satoko, Mori, Kazuhiko, Abu Amero, Khaled, Hauser, Michael, Li, Zheng, Prakadeeswari, Gopalakrishnan, Bailey, Jessica N. Cooke, Cherecheanu, Alina Popa, Kang, Jae H, Nelson, Sarah, Hayashi, Ken, Manabe, Shin Ichi, Kazama, Shigeyasu, Zarnowski, Tomasz, Inoue, Kenji, Irkec, Murat, Coca Prados, Miguel, Sugiyama, Kazuhisa, Järvelä, Irma, Schlottmann, Patricio, Lerner, S. Fabian, Lamari, Hasnaa, Nilgün, Yildirim, Bikbov, Mukharram, Park, Ki Ho, Cha, Soon Cheol, Yamashiro, Kenji, Zenteno, Juan C, Jonas, Jost B, Kumar, Rajesh S, Perera, Shamira A, Chan, Anita S. Y, Kobakhidze, Nino, George, Ronnie, Vijaya, Lingam, Do, Tan, Edward, Deepak P, de Juan Marcos, Lourde, Pakravan, Mohammad, Moghimi, Sasan, Ideta, Ryuichi, Bach Holm, Daniella, Kappelgaard, Per, Wirostko, Barbara, Thomas, Samuel, Gaston, Daniel, Bedard, Karen, Greer, Wenda L, Yang, Zhenglin, Chen, Xueyi, Huang, Lulin, Sang, Jinghong, Jia, Hongyan, Jia, Liyun, Qiao, Chunyan, Zhang, Hui, Liu, Xuyang, Zhao, Bowen, Wang, Ya Xing, Xu, Liang, Leruez, Stéphanie, Reynier, Pascal, Chichua, George, Tabagari, Sergo, Uebe, Steffen, Zenkel, Matthia, Berner, Daniel, Mossböck, Georg, Weisschuh, Nicole, Hoja, Ursula, Welge Luessen, Ulrich Christoph, Mardin, Christian, Founti, Panayiota, Chatzikyriakidou, Anthi, Pappas, Theofani, Anastasopoulos, Eleftherio, Lambropoulos, Alexandro, Ghosh, Arkasubhra, Shetty, Rohit, Porporato, Natalia, Saravanan, Vijayan, Venkatesh, Rengaraj, Shivkumar, Chandrashekaran, Kalpana, Narendran, Sarangapani, Sripriya, Kanavi, Mozhgan R, Beni, Afsaneh Naderi, Yazdani, Shahin, Lashay, Alireza, Naderifar, Homa, Khatibi, Nassim, Fea, Antonio, Lavia, Carlo, Dallorto, Laura, Rolle, Teresa, Frezzotti, Paolo, Paoli, Daniela, Salvi, Erika, Manunta, Paolo, Mori, Yosai, Miyata, Kazunori, Higashide, Tomomi, Chihara, Etsuo, Ishiko, Satoshi, Yoshida, Akitoshi, Yanagi, Masahide, Kiuchi, Yoshiaki, Ohashi, Tsutomu, Sakurai, Toshiya, Sugimoto, Takako, Chuman, Hideki, Aihara, Makoto, Inatani, Masaru, Miyake, Masahiro, Gotoh, Norimoto, Matsuda, Fumihiko, Yoshimura, Nagahisa, Ikeda, Yoko, Ueno, Morio, Sotozono, Chie, Jeoung, Jin Wook, Sagong, Min, Park, Kyu Hyung, Ahn, Jeeyun, Cruz Aguilar, Marisa, Ezzouhairi, Sidi M, Rafei, Abderrahman, Chong, Yaan Fun, Ng, Xiao Yu, Goh, Shuang Ru, Chen, Yueming, Yong, Victor H. K, Khan, Muhammad Imran, Olawoye, Olusola O, Ashaye, Adeyinka O, Ugbede, Idakwo, Onakoya, Adeola, Kizor Akaraiwe, Nkiru, Teekhasaenee, Chaiwat, Suwan, Yanin, Supakontanasan, Wasu, Okeke, Suhanya, Uche, Nkechi J, Asimadu, Ifeoma, Ayub, Humaira, Akhtar, Farah, Kosior Jarecka, Ewa, Lukasik, Urszula, Lischinsky, Ignacio, Castro, Vania, Grossmann, Rodolfo Perez, Megevand, Gordana Sunaric, Roy, Sylvain, Dervan, Edward, Silke, Eoin, Rao, Aparna, Sahay, Priti, Fornero, Pablo, Cuello, Osvaldo, Sivori, Delia, Zompa, Tamara, Mills, Richard A, Souzeau, Emmanuelle, Mitchell, Paul, Wang, Jie Jin, Hewitt, Alex W, Coote, Michael, Crowston, Jonathan G, Astakhov, Sergei Y, Akopov, Eugeny L, Emelyanov, Anton, Vysochinskaya, Vera, Kazakbaeva, Gyulli, Fayzrakhmanov, Rinat, Al Obeidan, Saleh A, Owaidhah, Ohoud, Aljasim, Leyla Ali, Chowbay, Balram, Foo, Jia Nee, Soh, Raphael Q, Sim, Kar Seng, Xie, Zhicheng, Cheong, Augustine W. O, Mok, Shi Qi, Soo, Hui Meng, Chen, Xiao Yin, Peh, Su Qin, Heng, Khai Koon, Husain, Rahat, Ho, Su Ling, Hillmer, Axel M, Cheng, Ching Yu, Escudero Domínguez, Francisco A, González Sarmiento, Rogelio, Martinon Torres, Frederico, Salas, Antonio, Pathanapitoon, Kessara, Hansapinyo, Linda, Wanichwecharugruang, Boonsong, Kitnarong, Nari, Sakuntabhai, Anavaj, Nguyn, Hip X, Nguyn, Giang T. T, Nguyn, Trình V, Zenz, Werner, Binder, Alexander, Klobassa, Daniela S, Hibberd, Martin L, Davila, Sonia, Herms, Stefan, Nöthen, Markus M, Moebus, Susanne, Rautenbach, Robyn M, Ziskind, Ari, Carmichael, Trevor R, Ramsay, Michele, Álvarez, Lydia, García, Montserrat, González Iglesias, Héctor, Rodríguez Calvo, Pedro P, Cueto, Luis Fernández Vega, Oguz, Çilingir, Tamcelik, Nevbahar, Atalay, Eray, Batu, Bilge, Aktas, Dilek, Kasım, Burcu, Wilson, M. Roy, Coleman, Anne L, Liu, Yutao, Challa, Pratap, Herndon, Leon, Kuchtey, Rachel W, Kuchtey, John, Curtin, Karen, Chaya, Craig J, Crandall, Alan, Zangwill, Linda M, Wong, Tien Yin, Nakano, Masakazu, Kinoshita, Shigeru, den Hollander, Anneke I, Vesti, Eija, Fingert, John H, Lee, Richard K, Sit, Arthur J, Shingleton, Bradford J, Wang, Ningli, Cusi, Daniele, Qamar, Raheel, Kraft, Peter, Pericak Vance, Margaret A, Raychaudhuri, Soumya, Heegaard, Steffen, Kivelä, Tero, Reis, André, Kruse, Friedrich E, Weinreb, Robert N, Pasquale, Louis R, Haines, Jonathan L, Thorsteinsdottir, Unnur, Jonasson, Fridbert, Allingham, R. Rand, Milea, Dan, Ritch, Robert, Kubota, Toshiaki, Tashiro, Kei, Vithana, Eranga N, Micheal, Shazia, Topouzis, Foti, Craig, Jamie E, Dubina, Michael, Sundaresan, Periasamy, Stefansson, Kari, Wiggs, Janey L, Pasutto, Francesca, Khor, Chiea Chuen, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and University of Helsinki
Subjects: 0301 basic medicine, Male, Calcium Channels/genetics, Messenger, Medizin, PSEUDOEXFOLIATION SYNDROME, Genome-wide association study, BLOOD-PRESSURE, Disease, Exfoliation Syndrome, Eye, Exfoliation Syndrome/ethnology/genetics, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], 0302 clinical medicine, PARKINSONS-DISEASE, 80 and over, ta319, Missense mutation, Genetics, Aged, 80 and over, Amino Acid Oxidoreductases/genetics/physiology, Alleles, Amino Acid Oxidoreductases, Amino Acid Substitution, Asian Continental Ancestry Group, Calcium Channels, Cell Adhesion, Extracellular Matrix, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Haplotypes, Humans, Molecular Chaperones, RNA, Messenger, Spheroids, Cellular, Genome-Wide Association Study, Mutation, Missense, Point Mutation, Metaanalysis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, ALZHEIMERS-DISEASE, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Chaperones/biosynthesis/genetics, Biology, SYNONYMOUS MUTATIONS, ta3111, Article, 03 medical and health sciences, Asian People, Asian Continental Ancestry Group/genetics, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Allele, Risk factor, GENOME-WIDE ASSOCIATION, Eye/metabolism, Aged, Genetic association, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Haplotype, Individuals, Glaucoma, Odds ratio, Extracellular Matrix/metabolism, RNA, Messenger/biosynthesis, MACULAR DEGENERATION, RISK LOCI, eye diseases, COMMON SEQUENCE VARIANTS, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, 030221 ophthalmology & optometry, RNA, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cellular, Spheroids, Missense, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Polymorphisms, purl.org/pe-repo/ocde/ford#1.06.07 [https], INFLAMMATORY-BOWEL-DISEASE
Abstract: International audience; Exfoliation syndrome (XFS) is the commonest known risk factor for secondary glaucoma and a significant cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A have been previously associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results between populations,and to identify new variants associated with XFS. We identified a rare, protective allele at LOXL1 (p.407Phe, OR= 25, P=2.9 x 10-14) through deep resequencing of XFS cases and controls from 9 countries. This variant results in increased cellular adhesion strength compared to the wild-type (p.407Tyr) allele. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 x 10-8). Index variants at the new loci map to chromosomes 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS, and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.
Published: 2017

40. Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability

Author: Andrew Ratanatharathorn, Monica Uddin, Robert J. Ursano, Derek E. Wildman, Stephan Ripke, Nathan A. Kimbrel, Amstadter Ab, Mark W. Miller, John P. Rice, Ronald C. Kessler, Melanie E. Garrett, Guia Guffanti, Sandro Galea, Allison E. Ashley-Koch, Laura J. Bierut, Michael A. Hauser, Jennifer A. Sumner, Henry R. Kranzler, Jordan W. Smoller, Allison E. Aiello, Kerry J. Ressler, Anthony P. King, Bekh Bradley, Caroline M. Nievergelt, Joel Gelernter, Adam X. Maihofer, Hongyu Zhao, Dan J. Stein, Shareefa Dalvie, Mark J. Daly, Mark W. Logue, Eric O. Johnson, Andrea L. Roberts, Nancy L. Saccone, Chia-Yen Chen, Nicole R. Nugent, Lindsay A. Farrer, Karestan C. Koenen, Rachel Yehuda, Jonathan Ian Bisson, Jean C. Beckham, Rajendra A. Morey, Nastassja Koen, Israel Liberzon, Dewleen G. Baker, Murray B. Stein, Lynn M. Almli, Alicia R. Martin, and Laramie E. Duncan
Subjects: 0301 basic medicine, Male, Multifactorial Inheritance, Bipolar Disorder, Genome-wide association study, Medical and Health Sciences, Stress Disorders, Post-Traumatic, 0302 clinical medicine, Risk Factors, 2.1 Biological and endogenous factors, Posttraumatic Stress Disorder, Aetiology, Stress Disorders, African Americans, Psychiatry, Sex Characteristics, PTSD, Single Nucleotide, Biological Sciences, Middle Aged, Serious Mental Illness, Post-Traumatic Stress Disorder (PTSD), 3. Good health, Psychiatry and Mental health, Mental Health, Schizophrenia, Meta-analysis, Major depressive disorder, Original Article, Female, social and economic factors, Psychology, Clinical psychology, Adult, European Continental Ancestry Group, Single-nucleotide polymorphism, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten, Genetic correlation, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, Cellular and Molecular Neuroscience, Sex Factors, Clinical Research, 2.3 Psychological, Behavioral and Social Science, mental disorders, medicine, Genetics, Humans, Genetic Predisposition to Disease, Bipolar disorder, Polymorphism, Molecular Biology, Depressive Disorder, Depressive Disorder, Major, Whites, Prevention, Human Genome, Psychology and Cognitive Sciences, Major, Heritability, medicine.disease, R1, Brain Disorders, Black or African American, 030104 developmental biology, Case-Control Studies, Post-Traumatic, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h 2 SNP) for European-American females of 29% that is similar to h 2 SNP for schizophrenia and is substantially higher than h 2 SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD - for both European- and African-American individuals - and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for 1/410 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.
Published: 2017

41. Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: a multi-cohort analysis

Author: Douglas J Rhee, Bernard Rosner, Louis R. Pasquale, Yeunjoo E. Song, Hugues Aschard, Caroline C W Klaver, Allison E. Ashley-Koch, Jessica N. Cooke Bailey, Felipe A. Medeiros, Gadi Wollstein, Jonathan L. Haines, Pirro G. Hysi, Terry Gaasterland, Lisa A Hark, Richard K. Lee, Vikas Gulati, Douglas Vollrath, R. Rand Allingham, Margaret A. Pericak-Vance, Anthony P Khawaja, Julia E. Richards, William K. Scott, Murray H. Brilliant, Ching-Yu Cheng, Robert P. Igo, Joel S. Schuman, Daniel I. Chasman, Michael A. Hauser, Yutao Liu, Tony Realini, Robert N. Weinreb, Jae H. Kang, Robert Ritch, C.M. vanDuijn, Kuldev Singh, Sayoko E. Moroi, Arthur J. Sit, Donald L. Budenz, Peter Kraft, Donald J. Zack, John H. Fingert, Janey L. Wiggs, William G. Christen, Adriana I Iglesias, Shane Haven, Harvard Medical School [Boston] (HMS), Centre d'Études Biologiques de Chizé - UMR 7372 (CEBC), Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), King‘s College London, Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Singapore Eye Research Institute [Singapore] (SERI), Lawrence Livermore National Laboratory (LLNL), Epidemiology, Ophthalmology, Institut National de la Recherche Agronomique (INRA)-La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), and Université de Rennes (UR)-École normale supérieure - Rennes (ENS Rennes)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Male, 0301 basic medicine, Aging, Linkage disequilibrium, Intraocular pressure, genetic structures, Glaucoma, Blood Pressure, Genome-wide association study, Neurodegenerative, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Linkage Disequilibrium, 0302 clinical medicine, Medicine, Genetics (clinical), Genetics & Heredity, Genetics, [STAT.AP]Statistics [stat]/Applications [stat.AP], MESH: Genetic Predisposition to Disease, MESH: Blood Pressure, 3. Good health, Open-Angle, MESH: Linkage Disequilibrium, Female, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Glaucoma, Open-Angle, medicine.medical_specialty, Open angle glaucoma, Clinical Sciences, International Glaucoma Genetics Consortium, Genetic correlation, Article, 03 medical and health sciences, MESH: Intraocular Pressure, Ophthalmology, Humans, Genetic Predisposition to Disease, Eye Disease and Disorders of Vision, Intraocular Pressure, MESH: Humans, business.industry, Human Genome, Neurosciences, Heritability, medicine.disease, MESH: Male, eye diseases, 030104 developmental biology, Blood pressure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030221 ophthalmology & optometry, MESH: Glaucoma, Open-Angle, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, sense organs, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, MESH: Female
Abstract: Item does not contain fulltext Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95% confidence interval: 1.18 (1.14-1.21), P=1.8 x 10(-27)) for the former trait but no association for the latter (P=0.93). Next, we used linkage disequilibrium (LD) score regression, to provide genome-wide estimates of correlation between traits without the need for additional phenotyping. We also compared our genome-wide estimate of heritability between IOP and BP to an estimate based solely on direct measures of these traits in the Erasmus Rucphen Family (ERF; n=2519) study using Sequential Oligogenic Linkage Analysis Routines (SOLAR). LD score regression revealed high genetic correlation between IOP and POAG (48.5%, P=2.1 x 10(-5)); however, genetic correlation between IOP and diastolic BP (P=0.86) and between diastolic BP and POAG (P=0.42) were negligible. Using SOLAR in the ERF study, we confirmed the minimal heritability between IOP and diastolic BP (P=0.63). Overall, IOP shares genetic basis with POAG, whereas BP has limited shared genetic correlation with IOP or POAG.
Published: 2017

42. Differential DNA methylation patterns in human Schlemm's canal endothelial cells with glaucoma

Author: Jingwen, Cai, Michelle D, Drewry, Kristin, Perkumas, W Michael, Dismuke, Michael A, Hauser, W Daniel, Stamer, and Yutao, Liu
Subjects: Adult, Male, Primary Cell Culture, Epigenesis, Genetic, Aqueous Humor, Cell Adhesion, Humans, Intraocular Pressure, Aged, Lymphatic Vessels, Homeodomain Proteins, Endothelial Cells, Molecular Sequence Annotation, Tenascin, DNA Methylation, Middle Aged, Gene Ontology, Case-Control Studies, CpG Islands, Female, sense organs, T-Box Domain Proteins, Co-Repressor Proteins, Glaucoma, Open-Angle, Molecular Chaperones, Transcription Factors, Research Article
Abstract: Purpose Schlemm’s canal (SC) endothelial cells derived from donors with or without glaucoma showed different mechanical properties and gene expression. As an important contributor to the regulation of intraocular pressure (IOP) and pathogenesis of primary open-angle glaucoma (POAG), the heritable key epigenetic changes, methylation may play an important role in the physiologic function of SC cells. This study aims to identify differentially methylated CpG sites (DMSs) in primary cultures of human SC cells with or without glaucoma. Methods We examined the methylation pattern of seven strains of primary human cells (two glaucoma and five normal SC cell samples), which were isolated and characterized using established protocols. DNA methylation was profiled using Illumina Human Methylation 450 BeadChip. Raw data were extracted and exported using Illumina GenomeStudio software. After quantile normalization, DNA methylation data were analyzed using R package RnBeads in Bioconductor. DMSs were filtered with p ≤ 1E-5, methylation change ≥ 0.1, and false discovery rate ≤ 0.05. The closest genes and the location of each CpG site were annotated using R package FDb.InfiniumMethylation.hg19. Gene Ontology and pathway analysis was performed using WebGestalt. Selected DMSs were validated using the Zymo qMethyl kit. Results We used five non-glaucoma and two glaucomatous SC cell samples to profile genome-wide DNA methylation using Illumina Infinium Methylation BeadChips. Principle component analysis showed the separation between the glaucoma and control samples. After quality control and differential analysis, we identified 298 highly significant DMSs (p ≤ 1E-5). Among them, 221 DMSs were within 1 kb of a nearby gene. Gene Ontology analysis demonstrated significant enrichment in positive regulation of cell migration, negative regulation of endothelial cell proliferation, and stress fiber and actin filament bundles. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed enrichment in cell adhesion and gap junctions. Several glaucoma-related genes were identified, including TGFBR3, THBS1, PITX2, DAXX, TBX3, TNXB, ANGPT1, and PLEKHA7. We also examined differentially methylated regions (DMRs) near these CpG sites and identified significant DMRs in TBX3, TNXB1, DAXX, and PITX2. Conclusions This study represents the first genome-wide DNA methylation profiling in cultured human primary SC cells. The DMSs were enriched in the pathways related to outflow resistance. Several DMRs were validated in glaucoma-associated genes, further suggesting the role of DNA methylation in glaucoma development. This study could provide comprehensive understanding of DNA methylation in glaucoma and its effect on aqueous humor outflow.
Published: 2019

43. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

Author: Magali Haas, Nancy L. Saccone, Barbara O. Rothbaum, Jessica L. Maples-Keller, Aferdita Goci Uka, Soraya Seedat, Marie Bækvad-Hansen, Scott R. Sponheim, Sixto E. Sanchez, Nastassja Koen, Alma Dzubur-Kulenovic, Sonya B. Norman, Douglas Maurer, Julia S. Seng, Matig R. Mavissakalian, Wesley K. Thompson, Douglas L. Delahanty, Daniel F. Levey, Matthew S. Panizzon, Megan Brashear, Lindsay A. Farrer, Kenneth J. Ruggiero, John P. Rice, Robert H. Pietrzak, Lori A. Zoellner, Charles F. Gillespie, Lauren A.M. Lebois, Alaptagin Khan, Robert J. Ursano, Chia-Yen Chen, Yunpeng Wang, Karestan C. Koenen, Dewleen G. Baker, Joseph R. Calabrese, Jurjen J. Luykx, Andrew C. Heath, Shareefa Dalvie, Eric O. Johnson, Laura J. Bierut, Catrin Lewis, Henry R. Kranzler, Sarah McLeay, Caroline M. Nievergelt, Michelle F. Dennis, Miro Jakovljević, Merete Nordentoft, Michael A. Hauser, Alexander C. McFarlane, Mark J. Daly, Mark W. Logue, Ole Mors, Andrea L. Roberts, Adam X. Maihofer, S. Bryn Austin, Bart P. F. Rutten, Christiane Wolf, Erika J. Wolf, Sarah D. Linnstaedt, Janine D. Flory, Melanie E. Garrett, Christina M. Sheerin, Elbert Geuze, Alicia K. Smith, Christiaan H. Vinkers, Divya Mehta, Matthew Peverill, Bruce R. Lawford, Scott D. Gordon, José Miguel Caldas de Almeida, Miranda Van Hooff, Supriya Harnal, Edward S. Peters, Ross McD. Young, Derrick Silove, Jennifer A. Sumner, Gerome Breen, Allison E. Ashley-Koch, Michelle A. Williams, Antonia V. Seligowski, A.C. Bustamante, Dick Schijven, Joel Gelernter, Jordan W. Smoller, Nicholas G. Martin, Ananda B. Amstadter, Anthony P. King, Jonathan R. I. Coleman, Alexandra Evans, Alan L. Peterson, Kerry J. Ressler, Martin H. Teicher, Angela G. Junglen, Regina E. McGlinchey, Jonathan Ian Bisson, Adriana Lori, Karen-Inge Karstoft, Marti Jett, Bekh Bradley, Murray B. Stein, Michael J. Lyons, Nikolaos P. Daskalakis, Anders D. Børglum, Holly K. Orcutt, Sherry Winternitz, Carol E. Franz, Meaghan O'Donnell, Elizabeth A. Bolger, Seth G. Disner, William P. Milberg, Renato Polimanti, David Forbes, Alex O. Rothbaum, Edward J. Trapido, William S. Kremen, David M. Hougaard, Ronald C. Kessler, Dan J. Stein, Sian M. J. Hemmings, Tanja Jovanovic, Jonathan D. Wolff, Allison C. Provost, Stephan Ripke, Rachel Yehuda, Karmel W. Choi, Sandro Galea, Richard A. Bryant, Victoria B. Risbrough, Eric Vermetten, Dragan Babić, Ian Jones, Jürgen Deckert, Anders M. Dale, Rajendra A. Morey, Benjamin M. Neale, Melissa A. Polusny, Norah C. Feeny, Xue Jun Qin, Hongyu Zhao, Mark W. Miller, Guia Guffanti, Allison E. Aiello, Charles R. Marmar, Esmina Avdibegović, Torsten Klengel, Jennifer S. Stevens, Jean C. Beckham, Katharina Domschke, Katy Torres, Elliot C. Nelson, Laramie E. Duncan, Bozo Lugonja, Joanne Voisey, Milissa L. Kaufman, Ole A. Andreassen, Douglas E. Williamson, Paul A. Arbisi, Søren Bo Andersen, Thomas Werge, Monica Uddin, Katie A. McLaughlin, Zhewu Wang, Bizu Gelaye, Andrew Ratanatharathorn, Elizabeth G. Atkinson, Charles P. Morris, Preben Bo Mortensen, Christopher R. Erbes, Lynn M. Almli, Jonas Bybjerg-Grauholm, Alicia R. Martin, Nathan A. Kimbrel, Peter Roy-Byrne, Ariane Rung, Israel Liberzon, Leigh van den Heuvel, Marco P. Boks, Keith A. Young, Samuel A. McLean, Rasha Hammamieh, Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), MUMC+: MA Psychiatrie (3), Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and APH - Mental Health
Subjects: 0301 basic medicine, Male, Genetics of the nervous system, SYMPTOMS, Chemistry(all), LD SCORE REGRESSION, General Physics and Astronomy, Datasets as Topic, EFFICIENT, Genome-wide association study, PTSD, genome, Biochemistry, Genome-wide association studies, Stress Disorders, Post-Traumatic, 0302 clinical medicine, POSTTRAUMATIC-STRESS-DISORDER, African Continental Ancestry Group / genetics, HUMAN DEMOGRAPHIC HISTORY, Ubiquitin-Protein Ligases / genetics, lcsh:Science, Post-traumatic stress disorder (PTSD), Veterans, TRAUMA, Genetics, Multidisciplinary, 3. Good health, SNP HERITABILITY, Meta-analysis, Cohort, Behavioural genetics, Female, Ubiquitin-Protein Ligases, Science, Black People, Stress Disorders, Post-Traumatic / genetics, Biology, Physics and Astronomy(all), General Biochemistry, Genetics and Molecular Biology, Article, White People, 03 medical and health sciences, Sex Factors, Genetic variation, mental disorders, medicine, Journal Article, SNP, Humans, Genetic Predisposition to Disease, European Continental Ancestry Group / genetics, Veterans / statistics & numerical data, PARKINSON DISEASE, Post-traumatic stress disorder, Biochemistry, Genetics and Molecular Biology(all), General Chemistry, PROFILES, Heritability, medicine.disease, PREVENTION, 030104 developmental biology, Genetic Loci, lcsh:Q, Human genome, 030217 neurology & neurosurgery, Genetics and Molecular Biology(all), Genome-Wide Association Study
Abstract: The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations., Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.
Published: 2019

44. Genetic Correlations Between Diabetes and Glaucoma: An Analysis of Continuous and Dichotomous Phenotypes

Author: Janey L. Wiggs, C.M. vanDuijn, Vincent Laville, Adriana I Iglesias, Daniel I. Chasman, Bernard Rosner, Jessica N. Cooke Bailey, James F. Wilson, Michael A. Hauser, Jae H. Kang, William G. Christen, Christopher J Hammond, Hugues Aschard, Puya Gharahkhani, John H. Fingert, Alex W. Hewitt, Stuart MacGregor, Frank B. Hu, Peter Kraft, Louis R. Pasquale, Robert P. Igo, Yeunjoo E. Song, David A. Mackey, Pirro G. Hysi, Jonathan L. Haines, UK Biobank, Anthony P Khawaja, Clara C. Cousins, Reka Nagy, Veronique Vitart, Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Edinburgh, Case Western Reserve University [Cleveland], Harvard T.H. Chan School of Public Health, QIMR Berghofer Medical Research Institute, University of Melbourne, University of Tasmania [Hobart, Australia] (UTAS), The University of Western Australia (UWA), King‘s College London, University of Oxford [Oxford], University of Iowa [Iowa City], Duke University [Durham], University of Cambridge [UK] (CAM), Icahn School of Medicine at Mount Sinai [New York] (MSSM), The Orkney Complex Disease Study was supported by the Chief Scientist Office of the Scottish Government (CZB/4/276, CZB/4/710), a Royal Society URF to Dr Wilson, the MRC Human Genetics Unit quinquennial programme 'QTL in Health and Disease,' Arthritis Research UK, and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947)., The Viking Health Study – Shetland (VIKING) was supported by the MRC Human Genetics Unit quinquennial programme grant 'QTL in Health and Disease.', European Project: 35103,EUROSPAN, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Oxford, Clinical Genetics, and Ophthalmology
Subjects: Male, Linkage disequilibrium, genetic structures, Glaucoma, Genome-wide association study, Type 2 diabetes, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Incidence, Aged, 80 and over, 2. Zero hunger, MESH: Aged, 0303 health sciences, [STAT.AP]Statistics [stat]/Applications [stat.AP], MESH: Middle Aged, Incidence, MESH: Tonometry, Ocular, Middle Aged, Pedigree, 3. Good health, Europe, Phenotype, MESH: Young Adult, Female, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Glaucoma, Open-Angle, MESH: Diabetes Mellitus, Type 2, Adult, medicine.medical_specialty, Adolescent, MESH: Pedigree, Biology, MESH: Phenotype, Genetic correlation, Article, Tonometry, Ocular, Young Adult, 03 medical and health sciences, MESH: Cross-Sectional Studies, SDG 3 - Good Health and Well-being, MESH: Intraocular Pressure, Genetic linkage, Ophthalmology, medicine, MESH: United States, Humans, Intraocular Pressure, Aged, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Adult, Heritability, medicine.disease, United States, Human genetics, eye diseases, MESH: Male, Cross-Sectional Studies, Diabetes Mellitus, Type 2, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Genome-Wide Association Study, 030221 ophthalmology & optometry, MESH: Glaucoma, Open-Angle, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, sense organs, MESH: Europe, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Female, Genome-Wide Association Study
Abstract: Purpose A genetic correlation is the proportion of phenotypic variance between traits that is shared on a genetic basis. Here we explore genetic correlations between diabetes- and glaucoma-related traits. Design Cross-sectional study. Methods We assembled genome-wide association study summary statistics from European-derived participants regarding diabetes-related traits like fasting blood sugar (FBS) and type 2 diabetes (T2D) and glaucoma-related traits (intraocular pressure [IOP], central corneal thickness [CCT], corneal hysteresis [CH], corneal resistance factor [CRF], cup-to-disc ratio [CDR], and primary open-angle glaucoma [POAG]). We included data from the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database, the UK Biobank, and the International Glaucoma Genetics Consortium. We calculated genetic correlation (rg) between traits using linkage disequilibrium score regression. We also calculated genetic correlations between IOP, CCT, and select diabetes-related traits based on individual level phenotype data in 2 Northern European population-based samples using pedigree information and Sequential Oligogenic Linkage Analysis Routines. Results Overall, there was little rg between diabetes- and glaucoma-related traits. Specifically, we found a nonsignificant negative correlation between T2D and POAG (rg = −0.14; P = .16). Using Sequential Oligogenic Linkage Analysis Routines, the genetic correlations between measured IOP, CCT, FBS, fasting insulin, and hemoglobin A1c were null. In contrast, genetic correlations between IOP and POAG (rg ≥ 0.45; P ≤ 3.0 × 10−4) and between CDR and POAG were high (rg = 0.57; P = 2.8 × 10−10). However, genetic correlations between corneal properties (CCT, CRF, and CH) and POAG were low (rg range −0.18 to 0.11) and nonsignificant (P ≥ .07). Conclusion These analyses suggest that there is limited genetic correlation between diabetes- and glaucoma-related traits.
Published: 2019

45. Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies novel methylation loci

Author: Nathan A. Kimbrel, Melanie E. Garrett, Amstadter Ab, Caroline M. Nievergelt, Xuejun Qin, Allison E. Ashley-Koch, B. J. Luft, Lei Wang, Naviaux Jc, Eric Vermetten, Jean C. Beckham, Kerry J. Ressler, Elbert Geuze, Seyma Katrinli, Adriana Lori, Adam X. Maihofer, Guia Guffanti, Christiaan H. Vinkers, Michael A. Hauser, Karestan C. Koenen, Maria Dennis, Monica Uddin, Mark W. Logue, Andrew Ratanatharathorn, Alicia K. Smith, Pei Fen Kuan, Sandro Galea, Kilaru, Robert K. Naviaux, Allison E. Aiello, Victoria B. Risbrough, Nagy A. Youssef, Marco P. Boks, Evelyn J. Bromet, Kun Li, Rutten Bpf, Nicole R. Nugent, Dewleen G. Baker, Murray B. Stein, Robert J. Ursano, Mark W. Miller, and Ronald C. Kessler
Subjects: Oncology, 0303 health sciences, medicine.medical_specialty, business.industry, Locus (genetics), Methylation, Epigenome, Immune dysregulation, medicine.disease_cause, behavioral disciplines and activities, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, CpG site, Meta-analysis, Internal medicine, DNA methylation, mental disorders, medicine, Epigenetics, business, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Differences in susceptibility to posttraumatic stress disorder (PTSD) may be related to epigenetic differences between PTSD cases and trauma-exposed controls. Such epigenetic differences may provide insight into the biological processes underlying the disorder. Here we describe the results of the largest DNA methylation meta-analysis of PTSD to date with data from the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup. Ten cohorts, military and civilian, contributed blood-derived DNA methylation data (HumanMethylation450 BeadChip) from 1,896 PTSD cases (42%) and trauma-exposed controls (58%). Utilizing a common QC and analysis strategy, we identified ten CpG sites associated with PTSD (9.61E-07AHRR) locus and were associated with lower DNA methylation in PTSD cases relative to controls. Interestingly, this association appeared to uncorrelated with smoking status and was most pronounced in non-smokers with PTSD. Additional evaluation of metabolomics data supported our findings and revealed that AHRR methylation associated with kynurenine levels, which were lower among subjects with PTSD relative to controls. Overall, this study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.
Published: 2019
Full Text: View/download PDF

46. An indirect comparison meta-analysis of AS03 and MF59 adjuvants in pandemic influenza A(H1N1)pdm09 vaccines

Author: David Muscatello, Annabel C.Y. Soh, Robin M. Turner, Dominic E. Dwyer, and Michael I. Hauser
Subjects: Male, Squalene, medicine.medical_specialty, medicine.medical_treatment, 030231 tropical medicine, alpha-Tocopherol, MF59, Polysorbates, Hemagglutinin Glycoproteins, Influenza Virus, medicine.disease_cause, Antibodies, Viral, 03 medical and health sciences, 0302 clinical medicine, Influenza A Virus, H1N1 Subtype, Adjuvants, Immunologic, Internal medicine, Influenza, Human, medicine, Influenza A virus, Humans, 030212 general & internal medicine, AS03, Seroconversion, General Veterinary, General Immunology and Microbiology, business.industry, Immunogenicity, Vaccination, Public Health, Environmental and Occupational Health, Hemagglutination Inhibition Tests, Vaccine efficacy, Drug Combinations, Infectious Diseases, Influenza Vaccines, Meta-analysis, Molecular Medicine, Female, business, Adjuvant
Abstract: BACKGROUND Although oil-in-water adjuvants improve pandemic influenza vaccine efficacy, AS03 versus MF59 adjuvant comparisons in A(H1N1)pdm09 pandemic vaccines are lacking. METHODS We conducted an indirect-comparison meta-analysis extracting published data from randomised controlled trials in literature databases (01/01/2009-09/09/2018), evaluating immunogenicity and safety of AS03- or MF59-adjuvanted vaccines. We conducted comparisons of log-transformed haemagglutination inhibition geometric mean titre ratio (GMTR; primary outcome) of different regimens of each adjuvant versus unadjuvanted counterparts. Then via test of subgroup differences, we indirectly compared different AS03 versus MF59 regimens. RESULTS We identified 22 publications with 10,734 participants. In adults, AS03-adjuvanted vaccines (3.75 µg haemagglutinin) achieved superior GMTR versus unadjuvanted vaccines (all four comparisons); MD = 0.56 (95%CI 0.33 to 0.80, p
Published: 2019

47. Contributors

Author: Ryan Abbott, Ahmed T. Ahmed, Martin Alda, Ananda B. Amstadter, Ole A. Andreassen, Victoria K. Arnet, Cedric Bardy, Csaba Barta, Bernhard T. Baune, Elisabeth R.B. Becker, Bettina H. Bewernick, Joanna M. Biernacka, Stefan Bleich, Marissa S. Blumenthal, Cristian Bonvicini, Chad A. Bousman, Lisa C. Brown, Christie L. Burton, Han Cao, Joanne S. Carpenter, Danielle Cath, Micah Cearns, Donald D. Chang, Alexander Charney, Christopher R.K. Ching, Kate M. Chitty, Liliana G. Ciobanu, Scott R. Clark, A.M. Cole, Jane L. Collinson, Lucía Colodro-Conde, A. Corvin, David R. Cotter, Shane P.M. Cross, Jacob J. Crouse, John F Cryan, Darina Czamara, Shareefa Dalvie, Franziska Degenhardt, Douglas L. Delahanty, Timothy G Dinan, Valsamma Eapen, Harris A. Eyre, Andreas J. Forstner, Helge Frieling, Mark A. Frye, Lillian J. Gehue, Daniel Geller, Nicholas Glozier, Beata R. Godlewska, Andrea N. Goldstein-Piekarski, Ilona Gorbovskaya, Hans Jörgen Grabe, Iria Grande, Paul Grant, Zarina Greenberg, Edna Grünblatt, Adam J. Guastella, Anand Gururajan, Tim Hahn, Alisha S.M. Hall, Blake A. Hamilton, Alfons O. Hamm, Catherine J. Harmer, Jessica Hartmann, Michael A. Hauser, Daniel F. Hermens, Ian B. Hickie, Frank Iorfino, Neda Jahanshad, Iris E. Jansen, Angela G. Junglen, Helmet T. Karim, Manreena Kaur, Nastassja Koen, Dagmar Koethe, Jim Lagopoulos, Rico S.Z. Lee, Sophie E. Legge, Douglas F. Levinson, F. Markus Leweke, Julio Licinio, David E.J. Linden, Jonathan C.W. Liu, Anita Lo, Falk W. Lohoff, Adriana Lori, Ulrike Lueken, Carlo Maj, Patrick D. McGorry, Roger S. McIntyre, Agnes B. McMahon, Divya Mehta, Cristina Mei, Rajendra A. Morey, Daniel J. Müller, Sharon L. Naismith, Barnaby Nelson, Alexandra Neyazi, Alissa Nichles, Caroline M. Nievergelt, Nicole R. Nugent, C. Ormond, Antonio F. Pardiñas, Seth W. Perry, Claudia Pisanu, Danielle Posthuma, Renee-Marie Ragguett, Cyrus Raji, Margarita Raygada, Owen M. Rennert, Charles F. Reynolds, Sophie Sabherwal, Estela Salagre, Pamela H. Saunders, Catia Scassellati, Thomas E. Schlaepfer, Lianne Schmaal, Klaus Oliver Schubert, Emanuel Schwarz, Elizabeth M. Scott, Jan Scott, Jonathan Sebat, Giovanni Severino, Christina Sheerin, Ajeet B. Singh, Balwinder Singh, Stephen F. Smagula, Olav B. Smeland, Alicia K. Smith, Jill L. Sorcher, Rachael Spooner, Alessio Squassina, Eli A. Stahl, Dan J. Stein, Fabian Streit, Patrick F. Sullivan, Jennifer A. Sumner, Paul M. Thompson, Ashleigh M. Tickell, Catherine Toben, Monica Uddin, Arshya Vahabzadeh, Linh K. Van, Margot P. van de Weijer, Odile A. van den Heuvel, Sandra Van der Auwera, Anouk H.A. Verboven, Eduard Vieta, Zoe Wainer, James T.R. Walters, Hunna J. Watson, Django White, Leanne M. Williams, Stephanie H. Witt, Yin Yao, Zeynep Yilmaz, Gwyneth Zai, and Natalia Zmicerevska
Published: 2019

48. Using natural conversations to classify autism with limited data: Age matters

Author: Evangelos Sariyanidi, Michael A. Hauser, Casey J. Zampella, Robert T. Schultz, Julia Parish-Morris, Birkan Tunç, and Edward S. Brodkin
Subjects: Multivariate statistics, media_common.quotation_subject, medicine.disease, Variation (linguistics), Autism spectrum disorder, medicine, Domain knowledge, Natural (music), Autism, Conversation, Psychology, media_common, Cognitive psychology, Spoken language
Abstract: Spoken language ability is highly heterogeneous in Autism Spectrum Disorder (ASD), which complicates efforts to identify linguistic markers for use in diagnostic classification, clinical characterization, and for research and clinical outcome measurement. Machine learning techniques that harness the power of multivariate statistics and non-linear data analysis hold promise for modeling this heterogeneity, but many models require enormous datasets, which are unavailable for most psychiatric conditions (including ASD). In lieu of such datasets, good models can still be built by leveraging domain knowledge. In this study, we compare two machine learning approaches: the first approach incorporates prior knowledge about language variation across middle childhood, adolescence, and adulthood to classify 6-minute naturalistic conversation samples from 140 age- and IQ-matched participants (81 with ASD), while the other approach treats all ages the same. We found that individual age-informed models were significantly more accurate than a single model tasked with building a common algorithm across age groups. Furthermore, predictive linguistic features differed significantly by age group, confirming the importance of considering age-related changes in language use when classifying ASD. Our results suggest that limitations imposed by heterogeneity inherent to ASD and from developmental change with age can be (at least partially) overcome using domain knowledge, such as understanding spoken language development from childhood through adulthood.
Published: 2019

49. Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye

Author: Mineo Ozaki, Marcelo T. Nicolela, Theofanis Pappas, Fotis Topouzis, Andrés Fernández-Vega Cueto, Panayiota Founti, Eray Atalay, Nilgun Yildirim, Chie Sotozono, Christina Keskini, Yosai Mori, Luis Fernández-Vega Cueto, Andrew C. Orr, Murat Irkec, Yuanhan Li, Deepak P. Edward, Satoko Nakano, Yury S. Astakhov, Tsutomu Ohashi, Daniel Gaston, George Chichua, Evangelia S Panagiotou, Ursula Schlötzer-Schrehardt, Jae H. Kang, Sergo Tabagari, Federico Martinón-Torres, Akitoshi Yoshida, Lesya M. Shuba, Masaru Inatani, Ken Hayashi, Takako Sugimoto, Shamira A. Perera, Takanori Mizoguchi, Kar Seng Sim, Friedrich E. Kruse, Shin-ichi Manabe, Andreas Giessl, Joseph Saunders, Ewa Kosior-Jarecka, Christian Y. Mardin, Wai Leong Tam, Hui Meng Soo, Makoto Aihara, Yoshiaki Kiuchi, Tomomi Higashide, Wee Yang Meah, Rahat Husain, Tin Aung, Sergei Y. Astakhov, Zheng Li, Dimitrios G. Mikropoulos, André Reis, Eleftherios Anastasopoulos, Jessica N. Cooke Bailey, Anastasios G. P. Konstas, Toshiya Sakurai, Dilek Aktas, Montserrat García, Bilge Batu, Hideki Chuman, Shigeru Kinoshita, Matthias Zenkel, Ying Swan Ho, Nevbahar Tamçelik, Masakazu Nakano, Jonathan L. Haines, Nino Kobakhidze, Kazuhiko Mori, Esther Kai Lay Peh, Francesca Pasutto, Georg Mossböck, Anthi Chatzikyriakidou, Robert P. Igo, Etsuo Chihara, Kazuhisa Sugiyama, Janey L. Wiggs, Michael V. Dubina, Shuwen Chen, Paul E Rafuse, Xiao Yin Chen, Trevor R. Carmichael, Kei Tashiro, Miguel Coca-Prados, Claus Hellerbrand, Shigeyasu Kazama, Çilingir Oguz, Alexandros Lambropoulos, Patrick Tan, Michael A. Hauser, Burcu Kasım, Michèle Ramsay, Morio Ueno, Kana Tokumo, Kenji Inoue, Robert Ritch, Tomasz Zarnowski, Toshiaki Kubota, Sonia Davila, Steffen Heegaard, Ryuichi Ideta, Lydia Álvarez, Yoko Ikeda, Chiea Chuen Khor, Susan Williams, Satoshi Ishiko, Louis R. Pasquale, Eugeny L. Akopov, Antonio Salas, Alina Popa-Cherecheanu, Monisha E. Nongpiur, Héctor González-Iglesias, Urszula Lukasik, Jia Nee Foo, Augustine Cheong, Zhenxun Wang, Mei Chin Lee, Anita Chan, and Kazunori Miyata
Subjects: Risk, Loxl1, medicine.medical_specialty, Glaucoma, Gene, 01 natural sciences, Exfoliation syndrome, 03 medical and health sciences, Low-Frequency, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Disease, 030212 general & internal medicine, 0101 mathematics, Exfoliation (botany), Exome sequencing, Original Investigation, business.industry, Protein, 010102 general mathematics, Case-control study, General Medicine, Odds ratio, medicine.disease, Pseudoexfoliation Syndrome, Susceptibility, Cohort, business
Abstract: IMPORTANCE Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. OBJECTIVE To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. DESIGN, SETTING, AND PARTICIPANTS A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. EXPOSURES Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. MAIN OUTCOMES AND MEASURES The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 x 10(-6). The secondary outcomes included biochemical enzymatic assays and gene expression analyses. RESULTS The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 x 10(-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4%[interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. CONCLUSIONS AND RELEVANCE In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings. National Research Foundation of SingaporeNational Research Foundation, Singapore [NRF-NRFI2018-01]; US National Eye Institute of the National Institutes of Health [R01 EY020928, P30 EY014104, UM1 CA186107, U01 CA167552, EY015473]; Glaucoma Research Foundation of Canada [X052, CIRG17may053]; National Medical Research Council of SingaporeNational Medical Research Council, Singapore The study was funded by grant NRF-NRFI2018-01 from the National Research Foundation of Singapore. Additional support was provided by grants R01 EY020928, P30 EY014104, UM1 CA186107, U01 CA167552, and EY015473 from the US National Eye Institute of the National Institutes of Health, funding from the Glaucoma Research Foundation of Canada, and grants X052 and CIRG17may053 from the National Medical Research Council of Singapore.
Published: 2021

50. Addressing ethical challenges in the Genetics Substudy of the National Eye Survey of Trinidad and Tobago (GSNESTT)

Author: Tasanee Braithwaite, Christine V.F. Carrington, Subash Sharma, Allana Roach, Elysse Marcellin, Juan P. Casas, R. Rand Allingham, Rupert R A Bourne, Michael A. Hauser, Aroon D. Hingorani, and Samuel Ramsewak
Subjects: 0301 basic medicine, lcsh:QH426-470, media_common.quotation_subject, Population, Human genomics, Pharmaceutical Science, Audit, 030105 genetics & heredity, Article, Literacy, 03 medical and health sciences, 0302 clinical medicine, Informed consent, Genetics, Medicine, 030212 general & internal medicine, education, Molecular Biology, media_common, Ethics, education.field_of_study, Community engagement, business.industry, Corporate governance, Capacity building, Comprehension, lcsh:Genetics, Trinidad and Tobago, ELSI, business, Biotechnology
Abstract: Background:\ud \ud The conduct of international collaborative genomics research raises distinct ethical challenges that require special consideration, especially if conducted in settings that are research-naïve or resource-limited. Although there is considerable literature on these issues, there is a dearth of literature chronicling approaches taken to address these issues in the field. Additionally no previous ethical guidelines have been developed to support similar research in Trinidad and Tobago.\ud \ud Methods:\ud \ud A literature review was undertaken to identify strategies used to address common ethical issues relevant to human genetics and genomics research in research-naïve or resource-limited settings. Strategies identified were combined with novel approaches to develop a culturally appropriate, multifaceted strategy to address potential challenges in the Genetics Substudy of the National Eye Survey of Trinidad and Tobago (GSNESTT).\ud \ud Results:\ud \ud Regarding the protection of study participants, we report a decision to exclude children as participants; the use of a Community Engagement and Sensitization Strategy to increase the genetic literacy of the target population; the involvement of local expertise to ensure cultural sensitivity and to address potential comprehension barriers in informed consent; and an audit of the informed consent process to ensure valid consent. Concerning the regulation of the research, we report on ethics approvals from relevant authorities; a Materials Transfer Agreement to guide sample ownership and export; and a Sample Governance Committee to oversee data use and data access. Finally regarding the protection of the interests of scientists from the host country, we report on capacity building efforts to ensure that local scientists have access to data collected through the project and appropriate recognition of their contributions in future publications.\ud \ud Conclusion:\ud \ud This paper outlines an ethical framework for the conduct of population-based genetics and genomics research in Trinidad and Tobago; highlights common issues arising in the field and strategies to address these.
Published: 2016

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Category

Publication Type

Journal

Database

Publisher

334 results on '"Michael A. Hauser"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources