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5 results on '"Hemmings, Sian M.J."'

1. Enhancing discovery of genetic variants for PTSD through integration of quantitative phenotypes and trauma exposure information

Author

Maihofer, Adam X., Choi, Karmel W., Coleman, Jonathan R.I., Daskalakis, Nikolaos P., Denckla, Christy A., Ketema, Elizabeth, Morey, Rajendra A., Polimanti, Renato, Ratanatharathorn, Andrew, Torres, Katy, Wingo, Aliza P., Zai, Clement C., Aiello, Allison E., Almli, Lynn M., Amstadter, Ananda B., Andersen, Soren B., Andreassen, Ole A., Arbisi, Paul A., Ashley-Koch, Allison E., Austin, S. Bryn, Avdibegovic, Esmina, Borglum, Anders D., Babic, Dragan, Bkvad-Hansen, Marie, Baker, Dewleen G., Beckham, Jean C., Bierut, Laura J., Bisson, Jonathan I., Boks, Marco P., Bolger, Elizabeth A., Bradley, Bekh, Brashear, Meghan, Breen, Gerome, Bryant, Richard A., Bustamante, Angela C., Bybjerg-Grauholm, Jonas, Calabrese, Joseph R., Caldas-de-Almeida, J.M., Chen, Chia-Yen, Dale, Anders M., Dalvie, Shareefa, Deckert, Jürgen, Delahanty, Douglas L., Dennis, Michelle F., Disner, Seth G., Domschke, Katharina, Duncan, Laramie E., Kulenovic, Alma Dzubur, Erbes, Christopher R., Evans, Alexandra, Farrer, Lindsay A., Feeny, Norah C., Flory, Janine D., Forbes, David, Franz, Carol E., Galea, Sandro, Garrett, Melanie E., Gautam, Aarti, Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles F., Goci, Aferdita, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Hauser, Michael A., Heath, Andrew C., Hemmings, Sian M.J., Hougaard, David Michael, Jakovljevic, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue-Jun, Karstoft, Karen-Inge, Kaufman, Milissa L., Kessler, Ronald C., Khan, Alaptagin, Kimbrel, Nathan A., King, Anthony P., Koen, Nastassja, Kranzler, Henry R., Kremen, William S., Lawford, Bruce R., Lebois, Lauren A.M., Lewis, Catrin, Liberzon, Israel, Linnstaedt, Sarah D., Logue, Mark W., Lori, Adriana, Lugonja, Bozo, Luykx, Jurjen J., Lyons, Michael J., Maples-Keller, Jessica L., Marmar, Charles, Martin, Nicholas G., Maurer, D., Mavissakalian, Matig R., McFarlane, Alexander, McGlinchey, Regina E., McLaughlin, Katie A., McLean, Samuel A., Mehta, Divya, Mellor, Rebecca, Michopoulos, Vasiliki, Milberg, William, Miller, Mark W., Morris, Charles Phillip, Mors, Ole, Mortensen, P.B., Nelson, Elliot C., Nordentoft, Merete, Norman, Sonya B., O'Donnell, Meaghan, Orcutt, Holly K., Panizzon, Matthew S., Peters, Edward S., Peterson, Alan L., Peverill, Matthew, Pietrzak, Robert H., Polusny, Melissa A., Rice, John P., Risbrough, Victoria B., Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, P., Ruggiero, Kenneth J., Rung, Ariane, Rutten, Bart P.F., Saccone, Nancy L., Sanchez, Sixto E., Schijven, Dick, Seedat, S., Seligowski, Antonia V., Seng, Julia S., Sheerin, Christina M., Silove, Derrick, Smith, Alicia K., Smoller, Jordan W., Sponheim, Scott R., Stein, Dan J., Stevens, Jennifer S., Teicher, Martin H., Thompson, Wesley K., Trapido, Edward, Uddin, Monica, Ursano, Robert J., Luella van den Heuvel, Leigh, Van Hooff, Miranda, Vermetten, Eric, Vinkers, Christiaan, Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Yehuda, Rachel, Young, Keith A., Young, Ross McD., Zhao, Hongyu, Zoellner, Lori A., Haas, Magali, Lasseter, Heather, Provost, Allison C., Salem, Rany M., Sebat, Jonathan, Shaffer, Richard A., Wu, Tianying, Ripke, Stephan, Daly, Mark J., Ressler, Kerry J., Koenen, Karestan C., Stein, Murray B., and Nievergelt, Caroline M.

Subjects
trauma, mental disorders, PheWAS, GWAS, PTSD, genetics, heritability, behavioral disciplines and activities
Abstract

Background\ud 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 (GWAS).\ud Methods\ud 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 LD-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 (MVP) GWAS of PTSD total symptoms.\ud Results\ud GWAS 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 out of these 9 PTSD loci were independently replicated in MVP.\ud Conclusion\ud Through using a quantitative trait measure of PTSD, we identify 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.

Published
2022

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

Author

Smith, Alicia K., Ratanatharathorn, Andrew, Maihofer, Adam X., Naviaux, Robert K., Aiello, Allison E., Amstadter, Ananda B., Ashley-Koch, Allison E., Baker, Dewleen G., Beckham, Jean C., Boks, Marco P., Bromet, Evelyn, Dennis, Michelle, Galea, Sandro, Garrett, Melanie E., Geuze, Elbert, Guffanti, Guia, Hauser, Michael A., Katrinli, Seyma, Kilaru, Varun, Kessler, Ronald C., Kimbrel, Nathan A., Koenen, Karestan C., Kuan, Pei Fen, Li, Kefeng, Logue, Mark W., Lori, Adriana, Luft, Benjamin J., Miller, Mark W., Naviaux, Jane C., Nugent, Nicole R., Qin, Xuejun, Ressler, Kerry J., Risbrough, Victoria B., Rutten, Bart P.F., Stein, Murray B., Ursano, Robert J., Vermetten, Eric, Vinkers, Christiaan H., Wang, Lin, Youssef, Nagy A., Marx, Christine, Grant, Gerry, Stein, Murray, Qin, Xue Jun, Jain, Sonia, McAllister, Thomas W., Zafonte, Ross, Lang, Ariel, Coimbra, Raul, Andaluz, Norberto, Shutter, Lori, George, Mark S., Brancu, Mira, Calhoun, Patrick S., Dedert, Eric, Elbogen, Eric B., Fairbank, John A., Hurley, Robin A., Kilts, Jason D., Kirby, Angela, Marx, Christine E., McDonald, Scott D., Moore, Scott D., Morey, Rajendra A., Naylor, Jennifer C., Rowland, Jared A., Swinkels, Cindy, Szabo, Steven T., Taber, Katherine H., Tupler, Larry A., Van Voorhees, Elizabeth E., Yoash-Gantz, Ruth E., Basu, Archana, Brick, Leslie A., Dalvie, Shareefa, Daskalakis, Nikolaos P., Ensink, Judith B.M., Hemmings, Sian M.J., Herringa, Ryan, Ikiyo, Sylvanus, Koen, Nastassja, Montalvo-Ortiz, Janitza, Nispeling, Danny, Pfeiffer, John, Schijven, Dick, Seedat, Soraya, Shinozaki, Gen, Sumner, Jennifer A., Swart, Patricia, Tyrka, Audrey, Van Zuiden, Mirjam, Wani, Agaz, Wolf, Erika J., Zannas, Anthony, Uddin, Monica, Nievergelt, Caroline M., ACS - Pulmonary hypertension & thrombosis, Graduate School, Adult Psychiatry, ARD - Amsterdam Reproduction and Development, Child Psychiatry, APH - Mental Health, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Global Health, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Anatomy and neurosciences, MUMC+: MA Psychiatrie (3), Psychiatrie & Neuropsychologie, and RS: MHeNs - R3 - Neuroscience

Subjects
Male, 0301 basic medicine, Oncology, VA Mid-Atlantic MIRECC Workgroup, General Physics and Astronomy, medicine.disease_cause, IMMUNOLOGY, Epigenesis, Genetic, Stress Disorders, Post-Traumatic, Cohort Studies, Epigenome, chemistry.chemical_compound, POSTTRAUMATIC-STRESS-DISORDER, 0302 clinical medicine, Basic Helix-Loop-Helix Transcription Factors, Medicine, DNA METHYLATION, Kynurenine, Stress Disorders, Multidisciplinary, ASSOCIATION, Methylation, Post-Traumatic Stress Disorder (PTSD), Anxiety Disorders, Military Personnel, Mental Health, CpG site, Meta-analysis, DNA methylation, Female, ARYL-HYDROCARBON RECEPTOR, medicine.medical_specialty, Science, behavioral disciplines and activities, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, AGE, Genetic, Clinical Research, Internal medicine, mental disorders, Genetics, Humans, EXPOSURE, Epigenetics, Post-traumatic stress disorder, PGC PTSD Epigenetics Workgroup, business.industry, PROFILES, General Chemistry, DNA Methylation, Immune dysregulation, Repressor Proteins, 030104 developmental biology, chemistry, Case-Control Studies, Post-Traumatic, Wounds and Injuries, Epigenetics analysis, business, 030217 neurology & neurosurgery, INTRuST Clinical Consortium, Epigenesis
Abstract

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD., 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

3. Serotonin transporter variants play a role in anxiety sensitivity in South African adolescents.

Author

Hemmings, Sian M.J., Martin, Lindi I., van der Merwe, Lize, Benecke, Rohan, Domschke, Katharina, and Seedat, Soraya

Subjects
*ANXIETY sensitivity, *TEENAGERS, *GENOTYPE-environment interaction, *SEROTONIN, *POST-traumatic stress disorder
Abstract

Objectives: Anxiety sensitivity (AS) has predictive potential for the development of anxiety disorders. We investigated the role that gene–environment (G × E) interactions, focussing on childhood trauma (CT) and selectedSLC6A4variants, play in modulating levels of AS in a South African adolescent population.Methods: All adolescents (n = 951) completed measures for AS and CT. SixSLC6A4polymorphisms were genotyped. G × E influences on AS levels were assessed using multiple linear regression models. Relevant confounders were included in all analyses.Results: Xhosa (n = 634) and Coloured (n = 317) participants were analysed independently of one another. The5-HTTLPR-rs25531L-Ghaplotype associated with reduced AS among Xhosa adolescents (P = 0.010). In addition, the rs1042173CC-genotype protected against increased levels of AS in Xhosa participants who had experienced increased levels of CT (P = 0.038). Coloured males homozygous for theS-allele had significantly increased levels of AS compared to Coloured males with at least oneL-allele (P = 0.016).Conclusions: This is the first study to be conducted on AS in adolescents from two ethnically diverse populations. Results indicate that theL-Ghaplotype confers protection against high AS levels in a Xhosa population. Furthermore, increased CT was found to protect against high levels of AS in Xhosa rs1042173CC-carriers. [ABSTRACT FROM PUBLISHER]

Published
2016
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4. Corrigendum to “Gender in obsessive–compulsive disorder: clinical and genetic findings” [Eur. Neuropsychopharmacol. 14/2 (2004) 105–113]

Author

Lochner, Christine, Hemmings, Sian M.J., Kinnear, Craig J., Moolman-Smook, Johanna C., Corfield, Valerie A., Knowles, James A., Niehaus, Dana J.H., and Stein, Dan J.

Subjects
*OBSESSIVE-compulsive disorder, *PHENOMENOLOGY, *COMORBIDITY, *AMINE oxidase, *MONOAMINE oxidase
Abstract

Background: There is increasing recognition that obsessive–compulsive disorder (OCD) is not a homogeneous entity. It has been suggested that gender may contribute to the clinical and biological heterogeneity of OCD. Methods: Two hundred and twenty patients (n=220; 107 male, 113 female) with DSM-IV OCD (age: 36.40±13.46) underwent structured interviews. A subset of Caucasian subjects (n=178), including subjects from the genetically homogeneous Afrikaner population (n=81), and of matched control subjects (n=161), was genotyped for polymorphisms in genes involved in monoamine function. Clinical and genetic data were statistically analyzed across gender. Results: Compared with females, males with OCD (1) had an earlier age of onset, and a trend toward having more tics and worse outcome, (2) had somewhat differing patterns of OCD symptomatology and axis I comorbidity, and (3) in the Caucasian group, were more likely to have the high activity T allele of the EcoRV variant of the monoamine oxidase A (MAO-A) gene compared to controls, and (4) in the Afrikaner subgroup, were more frequently homozygous for the G allele at the G861C variant of the 5HT1Dβ gene than controls. Females with OCD (1) reported more sexual abuse during childhood than males, (2) often noted changes in obsessive–compulsive symptoms in the premenstrual/menstrual period as well as during/shortly after pregnancy, and with menopause, and (3) in the Caucasian subgroup, were more frequently homozygous for the low activity C allele of the EcoRV variant of the MAO-A gene compared to controls, with this allele also more frequent in female patients than controls. Conclusion: This study supports the hypothesis that gender contributes to the clinical and biological heterogeneity of OCD. A sexually dimorphic pattern of genetic susceptibility to OCD may be present. Further work is, however, needed to delineate the mechanisms that are responsible for mediating the effects of gender. [Copyright &y& Elsevier]

Published
2004
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5. Gender in obsessive–compulsive disorder: clinical and genetic findings

Author

Lochner, Christine, Hemmings, Sian M.J., Kinnear, Craig J., Moolman-Smook, Johanna C., Corfield, Valerie A., Knowles, James A., Niehaus, Dana J.H., and Stein, Dan J.

Subjects
*OBSESSIVE-compulsive disorder, *GENETICS, *HETEROGENEITY, *GENETIC polymorphisms
Abstract

Background: There is increasing recognition that obsessive–compulsive disorder (OCD) is not a homogeneous entity. It has been suggested that gender may contribute to the clinical and biological heterogeneity of OCD. Methods: Two hundred and twenty patients (n=220; 107 male, 113 female) with DSM-IV OCD (age: 36.40±13.46) underwent structured interviews. A subset of Caucasian subjects (n=178), including subjects from the genetically homogeneous Afrikaner population (n=81), and of matched control subjects (n=161), was genotyped for polymorphisms in genes involved in monoamine function. Clinical and genetic data were statistically analyzed across gender. Results: Compared with females, males with OCD (1) had an earlier age of onset, and a trend toward having more tics and worse outcome, (2) had somewhat differing patterns of OCD symptomatology and axis I comorbidity, and (3) in the Caucasian group, were more likely to have the high activity T allele of the EcoRV variant of the monoamine oxidase A (MAO-A) gene compared to controls, and (4) in the Afrikaner subgroup, were more frequently homozygous for the C allele at the G861C variant of the 5HT1Dβ gene than controls. Females with OCD (1) reported more sexual abuse during childhood than males, (2) often noted changes in obsessive–compulsive symptoms in the premenstrual/menstrual period as well as during/shortly after pregnancy, and with menopause, and (3) in the Caucasian subgroup, were more frequently homozygous for the low activity C allele of the EcoRV variant of the MAO-A gene compared to controls, with this allele also more frequent in female patients than controls. Conclusion: This study supports the hypothesis that gender contributes to the clinical and biological heterogeneity of OCD. A sexually dimorphic pattern of genetic susceptibility to OCD may be present. Further work is, however, needed to delineate the mechanisms that are responsible for mediating the effects of gender. [Copyright &y& Elsevier]

Published
2004
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