Polygenic risk scores differentiate schizophrenia patients with toxoplasma gondii compared to toxoplasma seronegative patients
Schizophrenia (SCZ) is an etiologically heterogeneous disease with genetic and environmental risk factors (e.g., Toxoplasma gondii infection) differing among affected individuals. Distinguishing such risk factors may point to differences in pathophysiological pathways and facilitate the discovery of...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-05-01
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| Series: | Comprehensive Psychiatry |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0010440X21000146 |
| _version_ | 1818870714181091328 |
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| author | Adriana Lori Dimitrios Avramopoulos Alex W. Wang Jennifer Mulle Nicholas Massa Erica J. Duncan Abigail Powers Karen Conneely Charles F. Gillespie Tanja Jovanovic Kerry J. Ressler Brad D. Pearce |
| author_facet | Adriana Lori Dimitrios Avramopoulos Alex W. Wang Jennifer Mulle Nicholas Massa Erica J. Duncan Abigail Powers Karen Conneely Charles F. Gillespie Tanja Jovanovic Kerry J. Ressler Brad D. Pearce |
| author_sort | Adriana Lori |
| collection | DOAJ |
| description | Schizophrenia (SCZ) is an etiologically heterogeneous disease with genetic and environmental risk factors (e.g., Toxoplasma gondii infection) differing among affected individuals. Distinguishing such risk factors may point to differences in pathophysiological pathways and facilitate the discovery of individualized treatments. Toxoplasma gondii (TOXO) has been implicated in increasing the risk of schizophrenia. To determine whether TOXO-positive individuals with SCZ have a different polygenic risk burden than uninfected people, we applied the SCZ polygenic risk score (SCZ-PRS) derived from the Psychiatric GWAS Consortium separately to the TOXO-positive and TOXO-negative subjects with the diagnosis of SCZ as the outcome variable. The SCZ-PRS does not include variants in the major histocompatibility complex.Of 790 subjects assessed for TOXO, the 662 TOXO-negative subjects (50.8% with SCZ) reached a Bonferroni corrected significant association (p = 0.00017, R2 = 0.023). In contrast, the 128 TOXO-positive individuals (53.1% with SCZ) showed no significant association (p = 0.354) for SCZ-PRS and had a much lower R2 (R2 = 0.007). To account for Type-2 error in the TOXO-positive dataset, we performed a random sampling of the TOXO-negative subpopulation (n = 130, repeated 100 times) to simulate equivalent power between groups: the p-value was <0.05 for SCZ-PRS 55% of the time but was rarely (6% of the time) comparable to the high p-value of the seropositive group at p > 0.354.We found intriguing evidence that the SCZ-PRS predicts SCZ in TOXO-negative subjects, as expected, but not in the TOXO-positive individuals. This result highlights the importance of considering environmental risk factors to distinguish a subgroup with independent or different genetic components involved in the development of SCZ. |
| first_indexed | 2024-12-19T12:11:24Z |
| format | Article |
| id | doaj.art-318d3ecc6f3c4eeb8bd67e5e424c38a4 |
| institution | Directory Open Access Journal |
| issn | 0010-440X |
| language | English |
| last_indexed | 2024-12-19T12:11:24Z |
| publishDate | 2021-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Comprehensive Psychiatry |
| spelling | doaj.art-318d3ecc6f3c4eeb8bd67e5e424c38a42022-12-21T20:22:10ZengElsevierComprehensive Psychiatry0010-440X2021-05-01107152236Polygenic risk scores differentiate schizophrenia patients with toxoplasma gondii compared to toxoplasma seronegative patientsAdriana Lori0Dimitrios Avramopoulos1Alex W. Wang2Jennifer Mulle3Nicholas Massa4Erica J. Duncan5Abigail Powers6Karen Conneely7Charles F. Gillespie8Tanja Jovanovic9Kerry J. Ressler10Brad D. Pearce11Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, 101 Woodruff Circle, GA 30322, USAInstitute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21205, USADept. of Epidemiology, Rollins School of Public Health; 1518 Clifton Rd., Atlanta, GA 30322, USA; Philadelphia College of Osteopathic Medicine, Suwanee, GA 30024, USADepartment of Human Genetics, Emory University, Atlanta, GA 30322, USADept. of Epidemiology, Rollins School of Public Health; 1518 Clifton Rd., Atlanta, GA 30322, USA; Atlanta Veterans Affairs Health Care System, Decatur, GA 30033, USADepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, 101 Woodruff Circle, GA 30322, USA; Atlanta Veterans Affairs Health Care System, Decatur, GA 30033, USADepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, 101 Woodruff Circle, GA 30322, USADepartment of Human Genetics, Emory University, Atlanta, GA 30322, USADepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, 101 Woodruff Circle, GA 30322, USAUniversity of Texas at Austin Dell Medical School, Austin, TX, USADepartment of Psychiatry, Harvard Medical School, Boston, MA 02115, USADept. of Epidemiology, Rollins School of Public Health; 1518 Clifton Rd., Atlanta, GA 30322, USA; Corresponding author at: Rollins School of Public Health, Emory University, Office: 1518 Clifton Rd. CNR 4049 (1518-002-AA), Atlanta, GA 30322, USA.Schizophrenia (SCZ) is an etiologically heterogeneous disease with genetic and environmental risk factors (e.g., Toxoplasma gondii infection) differing among affected individuals. Distinguishing such risk factors may point to differences in pathophysiological pathways and facilitate the discovery of individualized treatments. Toxoplasma gondii (TOXO) has been implicated in increasing the risk of schizophrenia. To determine whether TOXO-positive individuals with SCZ have a different polygenic risk burden than uninfected people, we applied the SCZ polygenic risk score (SCZ-PRS) derived from the Psychiatric GWAS Consortium separately to the TOXO-positive and TOXO-negative subjects with the diagnosis of SCZ as the outcome variable. The SCZ-PRS does not include variants in the major histocompatibility complex.Of 790 subjects assessed for TOXO, the 662 TOXO-negative subjects (50.8% with SCZ) reached a Bonferroni corrected significant association (p = 0.00017, R2 = 0.023). In contrast, the 128 TOXO-positive individuals (53.1% with SCZ) showed no significant association (p = 0.354) for SCZ-PRS and had a much lower R2 (R2 = 0.007). To account for Type-2 error in the TOXO-positive dataset, we performed a random sampling of the TOXO-negative subpopulation (n = 130, repeated 100 times) to simulate equivalent power between groups: the p-value was <0.05 for SCZ-PRS 55% of the time but was rarely (6% of the time) comparable to the high p-value of the seropositive group at p > 0.354.We found intriguing evidence that the SCZ-PRS predicts SCZ in TOXO-negative subjects, as expected, but not in the TOXO-positive individuals. This result highlights the importance of considering environmental risk factors to distinguish a subgroup with independent or different genetic components involved in the development of SCZ.http://www.sciencedirect.com/science/article/pii/S0010440X21000146 |
| spellingShingle | Adriana Lori Dimitrios Avramopoulos Alex W. Wang Jennifer Mulle Nicholas Massa Erica J. Duncan Abigail Powers Karen Conneely Charles F. Gillespie Tanja Jovanovic Kerry J. Ressler Brad D. Pearce Polygenic risk scores differentiate schizophrenia patients with toxoplasma gondii compared to toxoplasma seronegative patients Comprehensive Psychiatry |
| title | Polygenic risk scores differentiate schizophrenia patients with toxoplasma gondii compared to toxoplasma seronegative patients |
| title_full | Polygenic risk scores differentiate schizophrenia patients with toxoplasma gondii compared to toxoplasma seronegative patients |
| title_fullStr | Polygenic risk scores differentiate schizophrenia patients with toxoplasma gondii compared to toxoplasma seronegative patients |
| title_full_unstemmed | Polygenic risk scores differentiate schizophrenia patients with toxoplasma gondii compared to toxoplasma seronegative patients |
| title_short | Polygenic risk scores differentiate schizophrenia patients with toxoplasma gondii compared to toxoplasma seronegative patients |
| title_sort | polygenic risk scores differentiate schizophrenia patients with toxoplasma gondii compared to toxoplasma seronegative patients |
| url | http://www.sciencedirect.com/science/article/pii/S0010440X21000146 |
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