- Record: found
- Abstract: found
- Article: found
Potential causal association between gut microbiome and posttraumatic stress disorder
research-article
Author(s):
Qiang He
1 ,
Wenjing Wang
2 ,
Dingkang Xu
3 ,
Yang Xiong
4 ,
Chuanyuan Tao
1 ,
Chao You
1 ,
Lu Ma
1 ,
Junpeng Ma
1
,
,
the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group
Publication date (Electronic):
31 January 2024
Journal:
Translational Psychiatry
Publisher:
Nature Publishing Group UK
Read this article at
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Abstract
Background
The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR).
Methods
The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome.
Results
In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability.
Conclusion
Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.
Related collections
Most cited references52
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- Abstract: found
- Article: found
Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator
Jack Bowden, George Davey Smith, Philip C. Haycock … (2017)
ABSTRACT Developments in genome‐wide association studies and the increasing availability of summary genetic association data have made application of Mendelian randomization relatively straightforward. However, obtaining reliable results from a Mendelian randomization investigation remains problematic, as the conventional inverse‐variance weighted method only gives consistent estimates if all of the genetic variants in the analysis are valid instrumental variables. We present a novel weighted median estimator for combining data on multiple genetic variants into a single causal estimate. This estimator is consistent even when up to 50% of the information comes from invalid instrumental variables. In a simulation analysis, it is shown to have better finite‐sample Type 1 error rates than the inverse‐variance weighted method, and is complementary to the recently proposed MR‐Egger (Mendelian randomization‐Egger) regression method. In analyses of the causal effects of low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol on coronary artery disease risk, the inverse‐variance weighted method suggests a causal effect of both lipid fractions, whereas the weighted median and MR‐Egger regression methods suggest a null effect of high‐density lipoprotein cholesterol that corresponds with the experimental evidence. Both median‐based and MR‐Egger regression methods should be considered as sensitivity analyses for Mendelian randomization investigations with multiple genetic variants.
- Record: found
- Abstract: found
- Article: not found
Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases
Marie Verbanck, Chia-Yen Chen, Benjamin M. Neale … (2018)
Horizontal pleiotropy occurs when the variant has an effect on disease outside of its effect on the exposure in Mendelian randomization (MR). Violation of the ‘no horizontal pleiotropy’ assumption can cause severe bias in MR. We developed the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test to identify horizontal pleiotropic outliers in multi-instrument summary-level MR testing. We showed using simulations that MR-PRESSO is best suited when horizontal pleiotropy occurs in <50% of instruments. Next, we applied MR-PRESSO, along with several other MR tests to complex traits and diseases, and found that horizontal pleiotropy: (i) was detectable in over 48% of significant causal relationships in MR; (ii) introduced distortions in the causal estimates in MR that ranged on average from −131% to 201%; (iii) induced false positive causal relationships in up to 10% of relationships; and (iv) can be corrected in some but not all instances.
- Record: found
- Abstract: found
- Article: found
Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data
Genome-wide association studies, which typically report regression coefficients summarizing the associations of many genetic variants with various traits, are potentially a powerful source of data for Mendelian randomization investigations. We demonstrate how such coefficients from multiple variants can be combined in a Mendelian randomization analysis to estimate the causal effect of a risk factor on an outcome. The bias and efficiency of estimates based on summarized data are compared to those based on individual-level data in simulation studies. We investigate the impact of gene–gene interactions, linkage disequilibrium, and ‘weak instruments’ on these estimates. Both an inverse-variance weighted average of variant-specific associations and a likelihood-based approach for summarized data give similar estimates and precision to the two-stage least squares method for individual-level data, even when there are gene–gene interactions. However, these summarized data methods overstate precision when variants are in linkage disequilibrium. If the P-value in a linear regression of the risk factor for each variant is less than , then weak instrument bias will be small. We use these methods to estimate the causal association of low-density lipoprotein cholesterol (LDL-C) on coronary artery disease using published data on five genetic variants. A 30% reduction in LDL-C is estimated to reduce coronary artery disease risk by 67% (95% CI: 54% to 76%). We conclude that Mendelian randomization investigations using summarized data from uncorrelated variants are similarly efficient to those using individual-level data, although the necessary assumptions cannot be so fully assessed.
Author and article information
Contributors
Junpeng Ma:
ORCID: http://orcid.org/0009-0006-2293-1481
junpengma6@163.com
Journal
Journal ID (nlm-ta): Transl Psychiatry
Journal ID (iso-abbrev): Transl Psychiatry
Title:
Translational Psychiatry
Publisher:
Nature Publishing Group UK
(London
)
ISSN
(Electronic):
2158-3188
Publication date
(Electronic):
31
January
2024
Publication date PMC-release: 31
January
2024
Publication date Collection: 2024
Volume: 14
Electronic Location Identifier: 67
Affiliations
[1
]Department of Neurosurgery, West China Hospital, Sichuan University, (
https://ror.org/011ashp19)
37 Guoxue Lane, Wuhou District, Chengdu, 610041 Sichuan China
[2
]GRID grid.13291.38, ISNI 0000 0001 0807 1581, Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, West
China Hospital, , Sichuan University, ; 37 Guoxue Lane, Wuhou District, Chengdu, China
[3
]GRID grid.506261.6, ISNI 0000 0001 0706 7839, Department of Neurosurgery, Beijing Hospital, National Center of Gerontology, Institute
of Geriatric Medicine, , Chinese Academy of Medical Sciences, ; Beijing, China
[4
]GRID grid.13291.38, ISNI 0000 0001 0807 1581, Department of Urology, West China Hospital, , Sichuan University, ; Chengdu, China
[5
]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Psychiatry, , University of California, ; San Diego, CA USA
[6
]GRID grid.38142.3c, ISNI 000000041936754X, Department of Psychiatry, , Harvard Medical School, ; Boston, MA USA
[7
]Broad Institute, Stanley Center for Psychiatric Research, (
https://ror.org/05a0ya142)
Cambridge, MA USA
[8
]Institute of Psychiatry, Psychology and Neuroscience, Social, Genetic and Developmental
Psychiatry Centre, King’s College London, (
https://ror.org/0220mzb33)
London, UK
[9
]South African Medical Research Council Unit on Risk and Resilience in Mental Disorders,
Department of Psychiatry, University of Cape Town, (
https://ror.org/03p74gp79)
Cape Town, Western Cape South Africa
[10
]Department of Psychiatry and Behavioral Sciences, Stanford University, (
https://ror.org/00f54p054)
Stanford, CA USA
[11
]Veterans Affair Boston Healthcare System, National Center for PTSD, (
https://ror.org/04xv0vq46)
Boston, MA USA
[13
]Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University,
(
https://ror.org/03vek6s52)
Boston, MA USA
[14
]Department of Epidemiology, University of North Carolina at Chapel Hill, (
https://ror.org/0130frc33)
Chapel Hill, NC USA
[16
]Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics,
Richmond, VA USA
[17
]Research and Knowledge Centre, The Danish Veteran Centre, (
https://ror.org/01txtk792)
Ringsted, Denmark
[19
]GRID grid.410394.b, ISNI 0000 0004 0419 8667, Mental Health Service Line, , Minneapolis Veterans Affairs Health Care System, ; Minneapolis, MN USA
[21
]Division of Adolescent and Young Adult Medicine, Boston Children’s Hospital, (
https://ror.org/00dvg7y05)
Boston, MN USA
[22
]Department of Psychiatry, University Clinical Center of Tuzla, (
https://ror.org/0474ygz28)
Tuzla, Bosnia and Herzegovina
[24
]Department for Congenital Disorders, Statens Serum Institut, (
https://ror.org/0417ye583)
Copenhagen, Denmark
[25
]Department of Psychiatry and Behavioral Sciences, Duke University, (
https://ror.org/00py81415)
Durham, NC USA
[26
]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Department of Psychiatry, , Washington University in Saint Louis School of Medicine, ; St Louis, MO USA
[27
]Medical Research Council Centre for Psychiatric Genetics and Genomics, National Centre
for Mental Health, Cardiff University, (
https://ror.org/03kk7td41)
Cardiff, UK
[28
]GRID grid.7692.a, ISNI 0000000090126352, Utrecht Brain Center Rudolf Magnus, Department of Translational Neuroscience, , University Medical Center, ; Utrecht, The Netherlands
[29
]Centre for Integrative Sequencing, iSEQ, Aarhus University, (
https://ror.org/01aj84f44)
Aarhus, Denmark
[30
]GRID grid.484294.7, Mental Health Service Line, , Atlanta Veterans Affairs Health Care System, ; Decatur, Georgia
[31
]GRID grid.279863.1, ISNI 0000 0000 8954 1233, School of Public Health and Department of Epidemiology, , Louisiana State University Health Sciences Center, ; New Orleans, LA USA
[32
]National Institute for Health Research Biomedical Research Centre at the Maudsley,
King’s College London, (
https://ror.org/0220mzb33)
London, UK
[33
]Department of Psychology, University of New South Wales, (
https://ror.org/03r8z3t63)
Sydney, NSW Australia
[34
]GRID grid.214458.e, ISNI 0000000086837370, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine,
, University of Michigan Medical School, ; Ann Arbor, MI USA
[35
]GRID grid.241104.2, ISNI 0000 0004 0452 4020, Department of Psychiatry, , University Hospitals, ; Cleveland, OH USA
[36
]Chronic Diseases Research Centre [CEDOC], Lisbon Institute of Global Mental Health,
Lisbon, Portugal
[37
]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Radiology, Department of Neurosciences, , University of California, ; San Diego, CA USA
[38
]Psychiatric and Neurodevelopmental Genetics Unit [PNGU], Massachusetts General Hospital,
(
https://ror.org/002pd6e78)
Boston, MA USA
[39
]GRID grid.411760.5, ISNI 0000 0001 1378 7891, Center of Mental Health, Psychiatry, Psychosomatics and Psychotherapy, , University Hospital of Würzburg, ; Würzburg, Germany
[40
]Department of Psychological Sciences, Kent State University, (
https://ror.org/049pfb863)
Kent, OH USA
[41
]Duke Molecular Physiology Institute, Duke University, (
https://ror.org/00py81415)
Durham, NC USA
[42
]GRID grid.410394.b, ISNI 0000 0004 0419 8667, Research Service Line, , Minneapolis Veterans Affairs Health Care System, ; Minneapolis, MN USA
[43
]Department of Psychiatry and Psychotherapy, Faculty of Medicine, Medical Center,
University of Freiburg, (
https://ror.org/0245cg223)
Freiburg, Germany
[44
]University Clinical Center of Sarajevo, Department of Psychiatry, Sarajevo, Bosnia
and Herzegovina
[45
]GRID grid.410394.b, ISNI 0000 0004 0419 8667, Center for Care Delivery and Outcomes Research [CCDOR], , Minneapolis Veterans Affairs Health Care System, ; Minneapolis, MN USA
[46
]GRID grid.189504.1, ISNI 0000 0004 1936 7558, Department of Medicine, , Boston University School of Medicine, ; Boston, MA USA
[47
]Department of Psychological Sciences, Case Western Reserve University, (
https://ror.org/051fd9666)
Cleveland, OH USA
[48
]Department of Psychiatry, Icahn School of Medicine at Mount Sinai, (
https://ror.org/04a9tmd77)
New York, NY USA
[49
]Department of Psychiatry, University of Melbourne, (
https://ror.org/01ej9dk98)
Melbourne, VIC Australia
[50
]Department of Psychological and Brain Sciences, Boston University, (
https://ror.org/05qwgg493)
Boston, MA USA
[51
]GRID grid.418356.d, ISNI 0000 0004 0478 7015, Department of Psychiatry, US Department of Veterans Affairs, ; West Haven, CT USA
[52
]Research Center Military Mental Healthcare, Netherlands Ministry of Defence, Utrecht,
The Netherlands
[53
]Department of Psychiatry and Behavioral Sciences, Emory University, (
https://ror.org/03czfpz43)
Atlanta, Georgia
[54
]GRID grid.412416.4, ISNI 0000 0004 4647 7277, Department of Psychiatry, , University Clinical Centre of Kosovo, ; Prishtina, Republic of Kosovo
[55
]Department of Genetics and Computational Biology, Queensland Institute of Medical
Research (QIMR) Berghofer Medical Research Institute, (
https://ror.org/004y8wk30)
Brisbane, QLD Australia
[56
]GRID grid.420094.b, ISNI 0000 0000 9341 8465, US Army Center for Environmental Health Research, , Army Medical Research and Materiel Command, ; Fort Detrick, MD USA
[57
]Stanley Center for Psychiatric Research, Broad Institute, (
https://ror.org/05a0ya142)
Cambridge, MA USA
[58
]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Department of Genetics, , Washington University in Saint Louis School of Medicine, ; St Louis, MO USA
[59
]Department of Psychiatry, Stellenbosch University Faculty of Medicine and Health
Sciences, (
https://ror.org/05bk57929)
Cape Town, South Africa
[60
]GRID grid.412688.1, ISNI 0000 0004 0397 9648, Department of Psychiatry, , University Hospital Center of Zagreb, ; Zagreb, Croatia
[61
]GRID grid.62562.35, ISNI 0000000100301493, Behavioral Health and Criminal Justice Division, , Research Triangle Institute International, ; Research Triangle Park, NC USA
[62
]GRID grid.38142.3c, ISNI 000000041936754X, Department of Health Care Policy, , Harvard Medical School, ; Boston, MA USA
[63
]GRID grid.214458.e, ISNI 0000000086837370, Department of Psychiatry, , University of Michigan Medical School, ; Ann Arbor, MI USA
[64
]South Africa Medical Research Council Unit on Risk and Resilience in Mental Disorders,
University of Cape Town, (
https://ror.org/03p74gp79)
Cape Town, South Africa
[65
]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Department of Psychiatry, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
[66
]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Psychiatry and Department of Family Medicine and Public Health, , University of California, ; San Diego, CA USA
[67
]Queensland University of Technology, Institute of Health and Behavioral Innovation,
(
https://ror.org/03pnv4752)
Brisbane, QLD Australia
[68
]GRID grid.410711.2, ISNI 0000 0001 1034 1720, Department of Anesthesiology, , University of North Carolina Institute for Trauma Recovery, ; Chapel Hill, NC USA
[69
]Department of Gynecology and Obstetrics, Emory University, (
https://ror.org/03czfpz43)
Atlanta, Georgia
[70
]Utrecht Brain Center Rudolf Magnus, Department of Psychiatry, University Medical
Center, (
https://ror.org/013v7fk41)
Las Vegas, NV USA
[74
]Department of Psychiatry, University of Adelaide, (
https://ror.org/00892tw58)
Adelaide, SA Australia
[78
]Faculty of Health, Queensland University of Technology, (
https://ror.org/03pnv4752)
Brisbane, QLD Australia
[79
]Psychosis Research Unit, Aarhus University Hospital, (
https://ror.org/040r8fr65)
Risskov, Denmark
[80
]Centre for Integrated Register-Based Research, Aarhus University, (
https://ror.org/01aj84f44)
Aarhus, Denmark
[81
]GRID grid.452548.a, ISNI 0000 0000 9817 5300, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, ; Aarhus, Denmark
[82
]Executive Division, National Center for Posttraumatic Stress Disorder, White River
Junction, Hartford, VT USA
[83
]Department of Psychology, Northern Illinois University, (
https://ror.org/012wxa772)
DeKalb, IL USA
[84
]Department of Psychology, University of Texas, (
https://ror.org/01kd65564)
San Antonio, TX USA
[85
]Department of Psychology, University of Washington, (
https://ror.org/00cvxb145)
Seattle, WA USA
[86
]US Department of Veterans Affairs National Center for Posttraumatic Stress Disorder,
(
https://ror.org/04xv0vq46)
West Haven, CT USA
[87
]GRID grid.410394.b, ISNI 0000 0004 0419 8667, Department of Mental Health, , Minneapolis Veterans Affairs Health Care System, ; Minneapolis, MN USA
[88
]Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard
University, (
https://ror.org/03vek6s52)
Cambridge, MA USA
[89
]Department of Nursing and Department of Psychiatry, Medical University of South Carolina,
(
https://ror.org/012jban78)
Charleston, SC USA
[90
]GRID grid.279863.1, ISNI 0000 0000 8954 1233, School of Medicine and Department of Physiology, , Louisiana State University Health Sciences Center, ; New Orleans, LA USA
[91
]School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology,
Maastricht Universitair Medisch Centrum, (
https://ror.org/02jz4aj89)
Maastricht, The Netherlands
[92
]Facultad de Ciencias de la Salud, Department of Medicine, Universidad Peruana de
Ciencias Aplicadas, (
https://ror.org/047xrr705)
Lima, Peru
[93
]GRID grid.38142.3c, ISNI 000000041936754X, Department of Pediatrics, , Harvard Medical School, ; Boston, MA USA
[95
]Department of Psychiatry, University of New South Wales, (
https://ror.org/03r8z3t63)
Sydney, NSW Australia
[97
]Department of Medicine, Columbia University Medical Center, (
https://ror.org/01esghr10)
New York, NY USA
[99
]Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign,
(
https://ror.org/047426m28)
Urbana, IL USA
[100
]GRID grid.265436.0, ISNI 0000 0001 0421 5525, Department of Psychiatry, , Uniformed Services University, ; Bethesda, MD USA
[102
]GRID grid.5650.6, ISNI 0000000404654431, Department of Anatomy and Neurosciences, , Amsterdam Academic Medical Center, ; Amsterdam, The Netherlands
[103
]Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina,
(
https://ror.org/012jban78)
Charleston, SA USA
[106
]School of Psychology and Counseling, Queensland University of Technology, (
https://ror.org/03pnv4752)
Brisbane, QLD Australia
[108
]Department of Psychiatry and Behavioral Sciences, University of Washington, (
https://ror.org/00cvxb145)
Seattle, WA USA
Author information
Junpeng Ma
http://orcid.org/0009-0006-2293-1481
Article
Publisher ID: 2765DOI: 10.1038/s41398-024-02765-7
PMC ID: 10831060
PubMed ID: 38296956
SO-VID: db0fadde-7ced-4a88-93c8-88ee0e3a3935
Copyright © © The Author(s) 2024
License:
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
History
Date
received
: 1
August
2023
Date
revision received
: 5
January
2024
Date
accepted
: 10
January
2024
Categories
Subject:
Article
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ScienceOpen disciplines: Clinical Psychology & Psychiatry