Preprint / Version 1

Stratification of rheumatoid arthritis cohort using Ayurveda based deep phenotyping approach identifies novel genes in a GWAS

Authors

  • Garima Juyal aSchool of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India
  • Anuj Pandey bDepartment of Genetics, University of Delhi South Campus, New Delhi 110021, India
  • Sara Garcia cDepartment of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark
  • Sapna Negi dNational Institute of Pathology, Safdarjung Hospital Campus, New Delhi 110029, India
  • Ramneek Gupta cDepartment of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark
  • Uma Kumar eDepartment of Rheumatology, All India Institute of Medical Sciences, New Delhi 110029, India
  • Bheema Bhat fDepartment of Ayurveda, Holy Family Hospital, New Delhi 110025, India
  • Ramesh Juyal gNational Institute of Immunology, New Delhi 110067, India
  • BK Thelma bDepartment of Genetics, University of Delhi South Campus, New Delhi 110021, India

Keywords:

Rheumatoid arthritis, Ayurgenomics, Ayurveda, Genome-wide association study, P4 medicine

Abstract

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. Keywords: Rheumatoid arthritis, Ayurgenomics, Ayurveda, Genome-wide association study, P4 medicine Abbreviations: GWAS, Genome-wide association study; RA, Rheumatoid arthritis; P4 medicine, Predictive, Preventive, Personalized and Participatory medicine; SNPs, Single nucleotide polymorphisms; Trx, Thioredoxin; Cul3, Cullin E3 ubiquitin ligase; lncRNA, Long intergenic non-coding RNA; MAF, Minor allele frequency; HWE, Hardy-Weinberg equilibrium; QC, Quality control

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