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Stratification of rheumatoid arthritis cohort using Ayurveda based deep phenotyping approach identifies novel genes in a GWAS
BACKGROUND AND AIM: Genome wide association studies have scaled up both in terms of sample size and range of complex disorders investigated, but these have explained relatively little phenotypic variance. Of the several reasons, phenotypic heterogeneity seems to be a likely contributor for missing o...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259475/ https://www.ncbi.nlm.nih.gov/pubmed/35793592 http://dx.doi.org/10.1016/j.jaim.2022.100578 |
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author | Juyal, Garima Pandey, Anuj Garcia, Sara L. Negi, Sapna Gupta, Ramneek Kumar, Uma Bhat, Bheema Juyal, Ramesh C. Thelma, B.K. |
author_facet | Juyal, Garima Pandey, Anuj Garcia, Sara L. Negi, Sapna Gupta, Ramneek Kumar, Uma Bhat, Bheema Juyal, Ramesh C. Thelma, B.K. |
author_sort | Juyal, Garima |
collection | PubMed |
description | BACKGROUND AND AIM: Genome wide association studies have scaled up both in terms of sample size and range of complex disorders investigated, but these have explained relatively little phenotypic variance. Of the several reasons, phenotypic heterogeneity seems to be a likely contributor for missing out genetic associations of large effects. Ayurveda, the traditional Indian system of medicine is one such tool which adopts a holistic deep phenotyping approach and classifies individuals based on their body constitution/prakriti. We hypothesized that Ayurveda based phenotypic stratification of healthy and diseased individuals will allow us to achieve much desired homogeneous cohorts which would facilitate detection of genetic association of large effects. In this proof of concept study, we performed a genome wide association testing of clinically diagnosed rheumatoid arthritis patients and healthy controls, who were re-phenotyped into Vata, Pitta and Kapha predominant prakriti sub-groups. EXPERIMENTAL PROCEDURE: Genotypes of rheumatoid arthritis cases (Vata = 49; Pitta = 117; Kapha = 78) and controls (Vata = 33; Pitta = 175; Kapha = 85) were retrieved from the total genotype data, used in a recent genome-wide association study performed in our laboratory. A total of 528461 SNPs were included after quality control. Prakriti-wise genome-wide association analysis was employed. RESULTS AND CONCLUSION: This study identified (i) prakriti-specific novel disease risk genes of high effect sizes; (ii) putative candidates of novel therapeutic potential; and (iii) a good correlation between genetic findings and clinical knowledge in Ayurveda. Adopting Ayurveda based deep phenotyping may facilitate explaining hitherto undiscovered heritability in complex traits and may propel much needed progress in personalized medicine. |
format | Online Article Text |
id | pubmed-9259475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-92594752022-07-08 Stratification of rheumatoid arthritis cohort using Ayurveda based deep phenotyping approach identifies novel genes in a GWAS Juyal, Garima Pandey, Anuj Garcia, Sara L. Negi, Sapna Gupta, Ramneek Kumar, Uma Bhat, Bheema Juyal, Ramesh C. Thelma, B.K. J Ayurveda Integr Med Original Research Article BACKGROUND AND AIM: Genome wide association studies have scaled up both in terms of sample size and range of complex disorders investigated, but these have explained relatively little phenotypic variance. Of the several reasons, phenotypic heterogeneity seems to be a likely contributor for missing out genetic associations of large effects. Ayurveda, the traditional Indian system of medicine is one such tool which adopts a holistic deep phenotyping approach and classifies individuals based on their body constitution/prakriti. We hypothesized that Ayurveda based phenotypic stratification of healthy and diseased individuals will allow us to achieve much desired homogeneous cohorts which would facilitate detection of genetic association of large effects. In this proof of concept study, we performed a genome wide association testing of clinically diagnosed rheumatoid arthritis patients and healthy controls, who were re-phenotyped into Vata, Pitta and Kapha predominant prakriti sub-groups. EXPERIMENTAL PROCEDURE: Genotypes of rheumatoid arthritis cases (Vata = 49; Pitta = 117; Kapha = 78) and controls (Vata = 33; Pitta = 175; Kapha = 85) were retrieved from the total genotype data, used in a recent genome-wide association study performed in our laboratory. A total of 528461 SNPs were included after quality control. Prakriti-wise genome-wide association analysis was employed. RESULTS AND CONCLUSION: This study identified (i) prakriti-specific novel disease risk genes of high effect sizes; (ii) putative candidates of novel therapeutic potential; and (iii) a good correlation between genetic findings and clinical knowledge in Ayurveda. Adopting Ayurveda based deep phenotyping may facilitate explaining hitherto undiscovered heritability in complex traits and may propel much needed progress in personalized medicine. Elsevier 2022 2022-07-03 /pmc/articles/PMC9259475/ /pubmed/35793592 http://dx.doi.org/10.1016/j.jaim.2022.100578 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Article Juyal, Garima Pandey, Anuj Garcia, Sara L. Negi, Sapna Gupta, Ramneek Kumar, Uma Bhat, Bheema Juyal, Ramesh C. Thelma, B.K. Stratification of rheumatoid arthritis cohort using Ayurveda based deep phenotyping approach identifies novel genes in a GWAS |
title | Stratification of rheumatoid arthritis cohort using Ayurveda based deep phenotyping approach identifies novel genes in a GWAS |
title_full | Stratification of rheumatoid arthritis cohort using Ayurveda based deep phenotyping approach identifies novel genes in a GWAS |
title_fullStr | Stratification of rheumatoid arthritis cohort using Ayurveda based deep phenotyping approach identifies novel genes in a GWAS |
title_full_unstemmed | Stratification of rheumatoid arthritis cohort using Ayurveda based deep phenotyping approach identifies novel genes in a GWAS |
title_short | Stratification of rheumatoid arthritis cohort using Ayurveda based deep phenotyping approach identifies novel genes in a GWAS |
title_sort | stratification of rheumatoid arthritis cohort using ayurveda based deep phenotyping approach identifies novel genes in a gwas |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259475/ https://www.ncbi.nlm.nih.gov/pubmed/35793592 http://dx.doi.org/10.1016/j.jaim.2022.100578 |
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