35
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Meta-analysis of genome-wide SNP- and pathway-based associations for facets of neuroticism

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Neuroticism is a heritable personality trait that is comprised of distinct sub-factors, or facets. Sub-factors of neuroticism are linked to different emotional states or psychiatric symptoms and studying the genetic variants associated with these facets may help reveal the biological mechanisms underlying psychiatric disorders. In the present study, a meta-analysis of genome-wide association studies for six facets of neuroticism was performed in 5584 participants from three cohorts. Additionally, a Gene Set Enrichment Analysis was conducted to find biological pathways associated with each facet. Six neuroticism facets (N1: anxiety, N2: angry hostility, N3: depression, N4: self-consciousness, N5: impulsivity and N6: vulnerability) were assessed using the Korean version of the Revised NEO Personality Inventory. In the single-nucleotide polymorphism-based analysis, results showed genome-wide significance for N2 within the MIR548H3 gene (rs1360001, P=4.14 × 10 −9). Notable genes with suggestive associations ( P<1.0 × 10 −6) were ITPR1 for N1, WNT7A for N2, FGF10 and FHIT for N3, DDR1 for N4, VGLL4 for N5 and PTPRD for N6. In the pathway-based analysis, the axon guidance pathway was identified to be associated with multiple facets of neuroticism (N2, N4 and N6). The focal adhesion and extracellular matrix receptor interaction pathways were significantly associated with N2 and N3. Our findings revealed genetic influences and biological pathways that are associated with facets of neuroticism.

          Related collections

          Most cited references42

          • Record: found
          • Abstract: found
          • Article: not found

          Wnt signaling in disease and in development.

          Roel Nusse (2005)
          The highly conserved Wnt secreted proteins are critical mediators of cell-to-cell signaling during development of animals. Recent biochemical and genetic analyses have led to significant insight into understanding how Wnt signals work. The catalogue of Wnt signaling components has exploded. We now realize that multiple extracellular, cytoplasmic, and nuclear components modulate Wnt signaling. Moreover, receptor-ligand specificity and multiple feedback loops determine Wnt signaling outputs. It is also clear that Wnt signals are required for adult tissue maintenance. Perturbations in Wnt signaling cause human degenerative diseases as well as cancer.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes

            Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism, schizophrenia and Tourette syndrome, including A2BP1, AUTS2, CNTNAP2 and IMMP2L. The ADHD CNV gene set was also significantly enriched for genes known to be important for psychological and neurological functions, including learning, behavior, synaptic transmission and central nervous system development. Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD. A deletion within the glutamate receptor gene, GRM5, was found in an affected parent and all three affected offspring whose ADHD phenotypes closely resembled those of the GRM5 null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Neuroticism and common mental disorders: meaning and utility of a complex relationship.

              Neuroticism's prospective association with common mental disorders (CMDs) has fueled the assumption that neuroticism is an independent etiologically informative risk factor. This vulnerability model postulates that neuroticism sets in motion processes that lead to CMDs. However, four other models seek to explain the association, including the spectrum model (manifestations of the same process), common cause model (shared determinants), state and scar models (CMD episode adds temporary/permanent neuroticism). To examine their validity we reviewed literature on confounding, operational overlap, stability and change, determinants, and treatment effects. None of the models is able to account for (virtually) all findings. The state and scar model cannot explain the prospective association. The spectrum model has some relevance, especially for internalizing disorders. Common causes are most important but the vulnerability model cannot be excluded although confounding of the prospective association by baseline symptoms and psychiatric history is substantial. In fact, some of the findings, such as interactions with stress and the small decay of neuroticism's effect over time, are consistent with the vulnerability model. We describe research designs that discriminate the remaining models and plea for deconstruction of neuroticism. Neuroticism is etiologically not informative yet but useful as an efficient marker of non-specified general risk.
                Bookmark

                Author and article information

                Journal
                J Hum Genet
                J. Hum. Genet
                Journal of Human Genetics
                Nature Publishing Group
                1434-5161
                1435-232X
                October 2017
                15 June 2017
                : 62
                : 10
                : 903-909
                Affiliations
                [1 ]Department of Biochemistry, School of Medicine, Ewha Womans University , Seoul, Korea
                [2 ]Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University , Seoul, Korea
                [3 ]Biostatistics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University , Seoul, Korea
                [4 ]Department of Health, Behavior and Society and Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD, USA
                [5 ]Department of Laboratory Medicine, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University , Seoul, Korea
                [6 ]Department of Occupational Medicine, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University , Seoul, Korea
                [7 ]Department of Family Medicine and Health Screening Center, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University , Seoul, Korea
                [8 ]Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital , Ansan, Korea
                [9 ]Department of Preventive Medicine, School of Medicine, Ajou University , Suwon, Korea
                [10 ]Department of Internal Medicine, School of Medicine, Ewha Womans University , Seoul, Korea
                Author notes
                [* ]Department of Biochemistry, School of Medicine, Ewha Womans University, Ewha Womans University Mokdong Hospital , 1070, Anyangcheon-ro, Yangcheon-Gu, Seoul 158-710, Korea. E-mail: hyung@ 123456ewha.ac.kr
                [11]

                These authors contributed equally to this work.

                Article
                jhg201761
                10.1038/jhg.2017.61
                5622119
                28615674
                fee08273-aef7-4cb6-b75c-c994e970216d
                Copyright © 2017 The Author(s)

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                History
                : 07 March 2017
                : 08 May 2017
                : 08 May 2017
                Categories
                Original Article

                Genetics
                Genetics

                Comments

                Comment on this article