DOI: https://doi.org/10.14710/jbtr.v7i3.12082

Patient-Driven Findings of Genetic Associations for PANS and PANDAS

1Scientists Canada, Canada

2Scientists USA, United States

Received: 19 Aug 2021; Revised: 3 Oct 2021; Accepted: 9 Nov 2021; Available online: 31 Dec 2021; Published: 31 Dec 2021.
Open Access Copyright (c) 2021 Journal of Biomedicine and Translational Research
Creative Commons License This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

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Abstract

Background: There are presently very few genetic studies for PANS (Pediatric Acute-Onset Neuropsychiatric Syndrome) or PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). More work in genetic associations for PANS and PANDAS (P/P) is needed to increase understanding of these debilitating childhood disorders that have a range of presentations.

Objective: This work represents a novel approach that aims to determine genetic associations between P/P and other diseases, disorders and traits (hereafter referred to as phenotypes).

Methods: Consumer genetic data (23andMe, AncestryDNA) for 155 patients with P/P were obtained from consenting parents over a period from 2018 to 2020. An analysis plan for this work was registered at Open Science Framework, additional genotypes imputed using Impute.me, and polygenic risk scores for 1,702 phenotypes calculated for each of the 155 P/P patients.

Results: One-sample t-tests performed across the 155 individual risk scores revealed that P/P is statistically significantly associated with 21 different groups of Single Nucleotide Polymorphisms (SNPs) that are in turn associated with 21 phenotypes. Some of the 21 phenotypes (see Table 3) are previously known to be related to or associated with P/P: a group of SNPs associated with Tourette’s Syndrome, and another group associated with Autism Spectrum Disorder or Schizophrenia, and a third associated with “feeling nervous” yielded t-tests with p values of 1.2x10-5, 1.2x10-11 and 1.0x10-5 respectively for association with the P/P data. This validated our analysis methodology. Our analysis also revealed novel genetic associations such as between P/P and plasma anti-thyroglobulin levels (p=1.3x10-7), between P/P and triglycerides (p=5.6x10-6), and between P/P and Lewy body disease (p=7.8x10-6), inviting further investigation into the underlying etiology of P/P.

Conclusion: P/P is associated with many phenotypes not previously recognized as being connected to P/P. Further work on these connections can lead to better understanding of P/P.

Note: This article has supplementary file(s).

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Polygenic Risk Z-scores and T-test Analyses of Diseases, Disorders and Traits for 155 PANS/PANDAS patients
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Keywords: ANS Genetic Associations; PANS Polygenic Risk Score; Consumer Genetics Tests Imputation
Funding: none

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Section: Original Research Articles
Language : EN
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  1. PANDAS physicians network [Internet]. Pandasppn.org. 2013 [cited 2021 Jun 2]. Available from: https://www.pandasppn.org/
  2. Chang K, Frankovich J, Cooperstock M, Cunningham MW, Latimer ME, Murphy TK, et al. Clinical evaluation of youth with pediatric acute-onset neuropsychiatric syndrome (PANS): recommendations from the 2013 PANS Consensus Conference. J Child Adolesc Psychopharmacol. 2015;25(1):3–13
  3. Fernell E, Sundin M, Fasth A, Dinkler L, Galazka M, Gillberg C, et al. Paediatric Acute onset Neuropsychiatric Syndrome: Exploratory study finds no evidence of HLA class II association but high rate of autoimmunity in first-degree relatives. Acta Paediatr [Internet]. 2021;(apa.15805). Available from: http://dx.doi.org/10.1111/apa.15805
  4. E. Swedo S. From research subgroup to clinical syndrome: Modifying the PANDAS criteria to describe PANS (pediatric acute-onset neuropsychiatric syndrome). Pediatr Ther. 2012;02(02):2
  5. Karacaoğlan G, Lüleyap Ü, Tahiroğlu AY, Pazarcı P, Yaman A, Çetiner S, et al. Streptokok enfeksiyonu ile ilişkili pediatrik otoimmün nöropsikiyatrik hastalık (PANDAS) ile insan lököksit antijen (HLA) ilişkisi. Cukurova Med J. 2019;44(1):52–8
  6. Luleyap HU, Onatoglu D, Yilmaz MB, Alptekin D, Tahiroglu AY, Cetiner S, et al. Association between pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections disease and tumor necrosis factor-α gene-308 g/a, -850 c/t polymorphisms in 4-12-year-old children in Adana/Turkey. Indian J Hum Genet. 2013;19(2):196–201
  7. Çelik GG, Taş DA, Tahiroglu AY, Erken E, Seydaoğlu G, Ray PÇ, et al. Mannose-binding lectin 2 gene polymorphism in PANDAS patients. Noro Psikiyatr Ars. 2019;56(2):99–105
  8. Trifiletti R, Lachman HM, Manusama O, Zheng D, Spalice A, Chiurazzi P, et al. Identification of ultra-rare genetic variants in Pediatric Acute Onset Neuropsychiatric Syndrome (PANS) by exome and whole genome sequencing [Internet]. bioRxiv. 2021 [cited 2021 Jun 25]. p. 2021.05.25.21257256. Available from: https://www.medrxiv.org/content/10.1101/2021.05.25.21257256v1
  9. Genetic association study for PANDAS and PANS: Phase 3. 2020 [cited 2021 Jun 25]; Available from: https://osf.io/53yve/
  10. Folkersen L, Pain O, Ingason A, Werge T, Lewis CM, Austin J. Impute.Me: An open-source, non-profit tool for using data from direct-to-consumer genetic testing to calculate and interpret polygenic risk scores. Front Genet. 2020;11:578
  11. NEPANS – PANS PANDAS Facts [Internet] Nepans.org [cited 2021 Jun 20]. Available from http://www.nepans.org/panspandas-info.html
  12. OSF [Internet]. Osf.io. [cited 2021 Jun 3]. Available from: https://osf.io/m2k6v/
  13. Calaprice D, Tona J, Parker-Athill EC, Murphy TK. A survey of pediatric acute-onset neuropsychiatric syndrome characteristics and course. J Child Adolesc Psychopharmacol. 2017;27(7):607–18
  14. OSF [Internet]. Osf.io. [cited 2021 Jun 2]. Available from: https://osf.io/ck5un/
  15. Docker Hub [Internet]. hub.docker.com. [cited 2021 Jun 2]. Available from: https://hub.docker.com/lassefolkersen/impute-me/
  16. Sala R, Amet L, Blagojevic-Stokic N, Shattock P, Whiteley P. Bridging the gap between physical health and autism spectrum disorder. Neuropsychiatr Dis Treat. 2020;16:1605–18
  17. Thiel A, Broocks A, Ohlmeier M, Jacoby GE, Schüssler G. Obsessive-compulsive disorder among patients with anorexia nervosa and bulimia nervosa. Am J Psychiatry. 1995;152(1):72–5
  18. Dunlop BW, Nemeroff CB. The role of dopamine in the pathophysiology of depression. Arch Gen Psychiatry. 2007;64(3):327–37
  19. Karagüzel EÖ, Arslan FC, Uysal EK, Demir S, Aykut DS, Tat M, et al. Blood levels of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha and cognitive functions in patients with obsessive compulsive disorder. Compr Psychiatry. 2019;89:61–6
  20. Brambilla F, Perna G, Bellodi L, Arancio C, Bertani A, Perini G, et al. Plasma interleukin-1 beta and tumor necrosis factor concentrations in obsessive-compulsive disorders. Biol Psychiatry. 1997;42(11):976–81
  21. Church AJ, Dale RC, Lees AJ, Giovannoni G, Robertson MM. Tourette’s syndrome: a cross sectional study to examine the PANDAS hypothesis. J Neurol Neurosurg Psychiatry. 2003;74(5):602–7

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