Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women
Open accessAbstract
Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder with a particularly high burden for women. Emerging evidence suggests PTSD may be more heritable among women and evidence from animal models and human correlational studies suggest connections between sex-linked biology and PTSD vulnerability, which may extend to the disorder's genetic architecture. We conducted a genome-wide association study (GWAS) of PTSD in a primarily African American sample of women from the Detroit Neighborhood Health Study (DNHS) and tested for replication in an independent cohort of primarily European American women from the Nurses Health Study II (NHSII). We genotyped 413 DNHS women - 94 PTSD cases and 319 controls exposed to at least one traumatic event - on the Illumina HumanOmniExpress BeadChip for >700,000 markers and tested 578 PTSD cases and 1963 controls from NHSII for replication. We performed a network-based analysis integrating data from GWAS-derived independent regions of association and the Reactome database of functional interactions. We found genome-wide significant association for one marker mapping to a novel RNA gene, lincRNA AC068718.1, for which we found suggestive evidence of replication in NHSII. Our network-based analysis indicates that our top GWAS results were enriched for pathways related to telomere maintenance and immune function. Our findings implicate a novel RNA gene, lincRNA AC068718.1, as risk factor for PTSD in women and add to emerging evidence that non-coding RNA genes may play a crucial role in shaping the landscape of gene regulation with putative pathological effects that lead to phenotypic differences.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PTSD in women is associated with an enrichment of genes involved in inflammatory pathways.
“Results from a single genome-wide association study of PTSD indicate that PTSD in women is associated with an enrichment of genes involved in inflammatory pathways (Guffanti et al, 2013).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Guffanti et al, 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
Self-citationModularity and community structure in networks
Newman, M. E. J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601602103 · Cited by 12,256 · see citing works
Posttraumatic Stress Disorder in the National Comorbidity Survey
Kessler, R. C. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950240066012 · Cited by 10,379 · see citing works
The development of a Clinician-Administered PTSD Scale
Blake, D. D., Weathers, F. W., Nagy, L. M., Kaloupek, D. G., Gusman, F. D., Charney, D. S., & Keane, T. M. (1995) · Journal of Traumatic Stress · doi:10.1002/jts.2490080106 · Cited by 5,024 · see citing works
Evolution and Functions of Long Noncoding RNAs
Ponting, C. P., Oliver, P. L., & Reik, W. (2009) · Cell · doi:10.1016/j.cell.2009.02.006 · Cited by 4,917 · see citing works
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821 · see citing works
Hindorff, L. A., Sethupathy, P., Junkins, H. A., Ramos, E. M., Mehta, J. P., Collins, F. S., & Manolio, T. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903103106 · Cited by 4,013 · see citing works
Accelerated telomere shortening in response to life stress
Epel, E. S., Blackburn, E. H., Lin, J., Dhabhar, F. S., Adler, N. E., Morrow, J. D., & Cawthon, R. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407162101 · Cited by 3,002 · see citing works
McLean, C. P., Asnaani, A., Litz, B. T., & Hofmann, S. G. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.03.006 · Cited by 2,519 · see citing works
Trauma and Posttraumatic Stress Disorder in the Community: The 1996 Detroit Area Survey of Trauma
Breslau, N., Kessler, R. C., Chilcoat, H. D., Schultz, L. R., Davis, G. C., & Andreski, P. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.7.626 · Cited by 2,407 · see citing works
Modular regulatory principles of large non-coding RNAs
Guttman, M., & Rinn, J. L. (2012) · Nature · doi:10.1038/nature10887 · Cited by 2,257 · see citing works
Resnick, H. S., Kilpatrick, D. G., Dansky, B. S., Saunders, B. E., & al, E. (1993) · Journal of Consulting and Clinical Psychology · doi:10.1037//0022-006x.61.6.984 · Cited by 1,868 · see citing works
Resnick, H. S., Kilpatrick, D. G., Dansky, B. S., Saunders, B. E., & Best, C. L. (1993) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.61.6.984 · Cited by 1,868 · see citing works
lincRNAs act in the circuitry controlling pluripotency and differentiation
Guttman, M., Donaghey, J., Carey, B. W., Garber, M. G., Grenier, J. K., Munson, G., Young, G., Lucas, A. B., Ach, R. A., Bruhn, L., et al. (2011) · Nature · doi:10.1038/nature10398 · Cited by 1,845 · see citing works
The impact of retrotransposons on human genome evolution
Cordaux, R., & Batzer, M. (2009) · Nature reviews genetics · doi:10.1038/nrg2640 · Cited by 1,691 · see citing works
Biological studies of post-traumatic stress disorder
Pitman, R. K., Rasmusson, A. M., Koenen, K. C., Shin, L. M., Orr, S. P., Gilbertson, M. W., Milad, M. R., & Liberzon, I. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3339 · Cited by 1,529 · see citing works
Self-citationDanese, A., Moffitt, T. E., Harrington, H., Milne, B. J., Polanczyk, G., Pariante, C. M., Poulton, R., & Caspi, A. (2009) · Archives of Pediatrics & Adolescent Medicine · doi:10.1001/archpediatrics.2009.214 · Cited by 1,165 · see citing works
<i>TRAF1–C5</i> as a Risk Locus for Rheumatoid Arthritis — A Genomewide Study
Plenge, R. M., Seielstad, M., Padyukov, L., Lee, A. T., Remmers, E. F., Ding, B., Liew, A., Khalili, H., Chandrasekaran, A., Davies, L. R. L., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa073491 · Cited by 823 · see citing works
Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor
Ressler, K. J., Mercer, K. B., Bradley, B., Jovanovic, T., Mahan, A., Kerley, K., Norrholm, S. D., Kilaru, V., Smith, A. K., Myers, A. J., et al. (2011) · Nature · doi:10.1038/nature09856 · Cited by 800 · see citing works
Epigenetic and immune function profiles associated with posttraumatic stress disorder
Uddin, M., Aiello, A. E., Wildman, D. E., Koenen, K. C., Pawelec, G., de los Santos, R., Goldmann, E., & Galea, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910794107 · Cited by 518 · see citing works
Self-citationHuman Alu RNA Is a Modular Transacting Repressor of mRNA Transcription during Heat Shock
Mariner, P. D., Walters, R. D., Espinoza, C. A., Drullinger, L. F., Wagner, S. D., Kugel, J. F., & Goodrich, J. A. (2008) · Molecular Cell · doi:10.1016/j.molcel.2007.12.013 · Cited by 479 · see citing works
Breslau, N., Chilcoat, H. D., Kessler, R. C., Peterson, E. L., & Lucia, V. C. (1999) · Psychological Medicine · doi:10.1017/s0033291799008612 · Cited by 429 · see citing works
Posttraumatic stress disorder in an urban population of young adults: risk factors for chronicity
Breslau, N., & Davis, G. C. (1992) · American Journal of Psychiatry · doi:10.1176/ajp.149.5.671 · Cited by 416 · see citing works
Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder
Smith, A. K., Conneely, K. N., Kilaru, V., Mercer, K. B., Weiss, T. E., Bradley, B., Tang, Y., Gillespie, C. F., Cubells, J. F., & Ressler, K. J. (2011) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31212 · Cited by 355 · see citing works
Lebrón‐Milad, K., & Milad, M. R. (2012) · Biology of Mood & Anxiety Disorders · doi:10.1186/2045-5380-2-3 · Cited by 298 · see citing works
Childhood trauma associated with short leukocyte telomere length in posttraumatic stress disorder
O'Donovan, A., Epel, E., Lin, J., Wolkowitz, O., Cohen, B., Maguen, S., Metzler, T., Lenoci, M., Blackburn, E., & Neylan, T. C. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.01.035 · Cited by 262 · see citing works
ENCODE whole-genome data in the UCSC Genome Browser: update 2012
Rosenbloom, K. R., Dreszer, T. R., Long, J. C., Malladi, V. S., Sloan, C. A., Raney, B. J., Cline, M., Karolchik, D., Barber, G. P., Clawson, H., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1012 · Cited by 256 · see citing works
Jendrzejewski, J., He, H., Radomska, H. S., Li, W., Tomšič, J., Liyanarachchi, S., Davuluri, R. V., Nagy, R. S., & de la Chapelle, A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205654109 · Cited by 247 · see citing works
Logue, M. W., Baldwin, C. T., Guffanti, G., Melista, E., Wolf, E. J., Reardon, A. F., Uddin, M., Wildman, D. E., Galea, S., Koenen, K. C., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.113 · Cited by 238 · see citing works
Self-citationSartor, C. E., McCutcheon, V. V., Pommer, N. E., Nelson, E. C., Grant, J. D., Duncan, A. E., Waldron, M., Bucholz, K. K., Madden, P. A. F., & Heath, A. C. (2010) · Psychological Medicine · doi:10.1017/s0033291710002072 · Cited by 221 · see citing works
Goldmann, E., Aiello, A., Uddin, M., Delva, J., Koenen, K., Gant, L. M., & Galea, S. (2011) · Journal of Traumatic Stress · doi:10.1002/jts.20705 · Cited by 185 · see citing works
Self-citationPace, T. W. W., Wingenfeld, K., Schmidt, I., Meinlschmidt, G., Hellhammer, D. H., & Heim, C. M. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.07.232 · Cited by 184 · see citing works
Cornelis, M. C., Nugent, N. R., Amstadter, A. B., & Koenen, K. C. (2010) · Current Psychiatry Reports · doi:10.1007/s11920-010-0126-6 · Cited by 178 · see citing works
Self-citationAdeyemo, A., & Rotimi, C. N. (2009) · Public Health Genomics · doi:10.1159/000218711 · Cited by 171 · see citing works
Genome-wide Association Study Identifies New Susceptibility Loci for Posttraumatic Stress Disorder
Xie, P., Kranzler, H. R., Yang, C., Zhao, H., Farrer, L. A., & Gelernter, J. E. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.04.013 · Cited by 166 · see citing works
Genomic gems: SINE RNAs regulate mRNA production
Ponicsan, S. L., Kugel, J. F., & Goodrich, J. A. (2010) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2010.01.004 · Cited by 118 · see citing works
Middeldorp, C. M., de Moor, M. H. M., McGrath, L. M., Gordon, S. D., Blackwood, D., Costa, P. T., Terracciano, A., Krueger, R. F., de Geus, E. J. C., Nyholt, D. R., et al. (2011) · Translational Psychiatry · doi:10.1038/tp.2011.45 · Cited by 105 · see citing works
Self-citationAlmli, L. M., Mercer, K. B., Kerley, K. A., Feng, H., Bradley, B., Conneely, K. N., & Ressler, K. J. (2013) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32145 · Cited by 101 · see citing works
Uddin, M., Chang, S., Zhang, C., Ressler, K. J., Mercer, K. B., Galea, S., Keyes, K. M., McLaughlin, K. A., Wildman, D. E., Aiello, A. E., et al. (2012) · Depression and Anxiety · doi:10.1002/da.22037 · Cited by 90 · see citing works
Self-citationKoenen, K. C., Vivo, I. D., Rich-Edwards, J. W., Smoller, J. W., Wright, R. J., & Purcell, S. (2009) · BMC Psychiatry · doi:10.1186/1471-244x-9-29 · Cited by 60 · see citing works
Self-citationThe Stressor Criterion for Posttraumatic Stress Disorder
Roberts, A. L., Dohrenwend, B. P., Aiello, A. E., Wright, R. J., Maercker, A. R. A., Galea, S., & Koenen, K. C. (2012) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.11m07054 · Cited by 57 · see citing works
Self-citationMikuls, T. R., Padala, P. R., Sayles, H. R., Yu, F., Michaud, K. D., Caplan, L., Kerr, G. S., Reimold, A. M., Cannon, G. W., Richards, J. S., et al. (2013) · Arthritis Care & Research · doi:10.1002/acr.21778 · Cited by 57 · see citing works
No association between ADCYAP1R1 and post-traumatic stress disorder in two independent samples
Chang, S.-C., Xie, P., Anton, R. F., Vivo, I. D., Farrer, L. A., Kranzler, H. R., Oslin, D., Purcell, S., Roberts, A. L., Smoller, J. W., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.118 · Cited by 55 · see citing works
Self-citationWang, L., Cao, C., Wang, R., Qing, Y., Zhang, J., & Zhang, X. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.01.010 · Cited by 55 · see citing works
Recent human evolution has shaped geographical differences in susceptibility to disease
Marigorta, U. M., Lao, Ó., Casals, F., Calafell, F., Morcillo-Suárez, C., Faria, R., Bosch, E., Serra, F., Bertranpetit, J., Dopazo, H., et al. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-55 · Cited by 31 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Post-traumatic stress disorder.
Yehuda, R., Hoge, C. W., McFarlane, A. C., Vermetten, E., Lanius, R. A., Nievergelt, C. M., Hobfoll, S. E., Koenen, K. C., Neylan, T. C., & Hyman, S. E. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.57 · Cited by 870 · see citing works
Self-citationInflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond
Michopoulos, V., Powers, A., Gillespie, C. F., Ressler, K. J., & Jovanovic, T. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.146 · Cited by 786 · see citing works
LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer
Wang, Y., Lu, J.-H., Wu, Q.-N., Jin, Y., Wang, D.-S., Chen, Y.-X., Liu, J., Luo, X.-J., Meng, Q., Pu, H.-Y., et al. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1105-0 · Cited by 507 · see citing works
Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man
Fenster, R. J., Lebois, L. A. M., Ressler, K. J., & Suh, J. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0039-7 · Cited by 456 · see citing works
Gender- and sex-based contributors to sex differences in PTSD
Christiansen, D. M., & Berke, E. T. (2020) · Current Psychiatry Reports · doi:10.1007/s11920-020-1140-y · Cited by 270 · see citing works
Maul, S., Giegling, I., Fabbri, C., Corponi, F., Serretti, A., & Rujescu, D. (2020) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32763 · Cited by 125 · see citing works
The genetics and epigenetics of PTSD: overview, recent advances, and future directions
Sheerin, C. M., Lind, M. J., Bountress, K. E., Nugent, N. R., & Amstadter, A. B. (2017) · Current Opinion in Psychology · doi:10.1016/j.copsyc.2016.09.003 · Cited by 118 · see citing works
DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression
Wingo, A. P., Almli, L. M., Stevens, J. S., Klengel, T., Uddin, M., Li, Y., Bustamante, A. C., Lori, A., Koen, N., Stein, D. J., et al. (2015) · Nature Communications · doi:10.1038/ncomms10106 · Cited by 98 · see citing works
Self-citationLogue, M. W., Smith, A. K., Baldwin, C., Wolf, E. J., Guffanti, G., Ratanatharathorn, A., Stone, A., Schichman, S. A., Humphries, D., Binder, E. B., et al. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.03.016 · Cited by 80 · see citing works
Self-citationRyan, J., Chaudieu, I., Ancelin, M.-L., & Saffery, R. (2016) · Epigenomics · doi:10.2217/epi-2016-0083 · Cited by 85 · see citing works
Almli, L. M., Stevens, J. S., Smith, A. K., Kilaru, V., Meng, Q., Flory, J., Abu‐Amara, D., Hammamieh, R., Yang, R., Mercer, K. B., et al. (2015) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32315 · Cited by 80 · see citing works
Mehta, D., Bruenig, D., Carrillo‐Roa, T., Lawford, B., Harvey, W., Morris, C. P., Smith, A. K., Binder, E. B., Young, R. M., & Voisey, J. (2017) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12778 · Cited by 78 · see citing works
Neuroimaging genetic approaches to Posttraumatic Stress Disorder
Lebois, L. A. M., Wolff, J. D., & Ressler, K. J. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.04.019 · Cited by 31 · see citing works
- Authors
- Guffanti, G., Galea, S., Yan, L., Roberts, A. L., Solovieff, N., Aiello, A. E., Smoller, J. W., De Vivo, I., Ranu, H., Uddin, M., Wildman, D. E., Purcell, S., & Koenen, K. C.
- Affiliations
- New York State Psychiatric Institute (US)
- Columbia University (US)
- Harvard University (US)
- Broad Institute (US)
- University of Michigan (US)
- Wayne State University (US)
- Corresponding author
- Koenen, Karestan C.
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 38
- Issue
- 12
- Pages
- 3029-3038
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC3844079
- OpenAlex
- W2127957059
- Cited by
- 120
- References
- 45
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 10 · 2021: 5 · 2020: 5 · 2019: 16 · 2018: 12 · 2017: 17 · 2016: 18 · 2015: 16 · 2014: 5
- FWCI
- 14.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01mh093612-03)
- National Institute of Mental Health (R01MH078928, RC1MH088283, R01-MH093612, MH-078928, MH088283, K24MH094614)
- National Institute on Drug Abuse (DA 022720, R01DA022720, DA 022720-S1)
- National Cancer Institute (CA50385, R01CA050385)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- post-traumatic stress disorder, long intergenic non-coding RNA, women, sex differences, genetic risk factors, telomere maintenance, immune function, African American women, European American women, trauma exposure
- MeSH terms
- Black or African American, Educational Status, Female, Gene Frequency, Genotype, Humans, Michigan, Middle Aged, Risk Factors, RNA, Socioeconomic Factors, Stress Disorders, Post-Traumatic, Case-Control Studies, Marital Status, Polymorphism, Single Nucleotide, Genome-Wide Association Study, RNA, Long Noncoding
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
