Genetic epidemiology of autoinflammatory disease variants in Indian population from 1029 whole genomes

Abhinav Jain; Rahul C Bhoyar; Kavita Pandhare; Anushree Mishra; Disha Sharma; Mohamed Imran; Vigneshwar Senthivel; Mohit Kumar Divakar; Mercy Rophina; Bani Jolly; Arushi Batra; Sumit Sharma; Sanjay Siwach; Arun G Jadhao; Nikhil V Palande; Ganga Nath Jha; Nishat Ashrafi; Prashant Kumar Mishra; Vidhya A K; Suman Jain; Debasis Dash; Nachimuthu Senthil Kumar; Andrew Vanlallawma; Ranjan Jyoti Sarma; Lalchhandama Chhakchhuak; Shantaraman Kalyanaraman; Radha Mahadevan; Sunitha Kandasamy; Pabitha B M; Raskin Erusan Rajagopal; Ezhil Ramya J; Nirmala Devi P; Anjali Bajaj; Vishu Gupta; Samatha Mathew; Sangam Goswami; Mohit Mangla; Savinitha Prakash; Kandarp Joshi; Meyakumla; Sreedevi S; Devarshi Gajjar; Ronibala Soraisham; Rohit Yadav; Yumnam Silla Devi; Aayush Gupta; Mitali Mukerji; Sivaprakash Ramalingam; Binukumar B K; Vinod Scaria; Sridhar Sivasubbu

doi:10.1186/s43141-021-00268-2

Genetic epidemiology of autoinflammatory disease variants in Indian population from 1029 whole genomes

J Genet Eng Biotechnol. 2021 Dec 14;19(1):183. doi: 10.1186/s43141-021-00268-2.

Authors

Abhinav Jain^{1

2}, Rahul C Bhoyar¹, Kavita Pandhare¹, Anushree Mishra¹, Disha Sharma¹, Mohamed Imran^{1

2}, Vigneshwar Senthivel^{1

2}, Mohit Kumar Divakar^{1

2}, Mercy Rophina^{1

2}, Bani Jolly^{1

2}, Arushi Batra^{1

2}, Sumit Sharma¹, Sanjay Siwach¹, Arun G Jadhao³, Nikhil V Palande⁴, Ganga Nath Jha⁵, Nishat Ashrafi⁵, Prashant Kumar Mishra⁶, Vidhya A K⁷, Suman Jain⁸, Debasis Dash^{1

2}, Nachimuthu Senthil Kumar⁹, Andrew Vanlallawma⁹, Ranjan Jyoti Sarma⁹, Lalchhandama Chhakchhuak¹⁰, Shantaraman Kalyanaraman¹¹, Radha Mahadevan¹¹, Sunitha Kandasamy¹¹, Pabitha B M¹¹, Raskin Erusan Rajagopal¹¹, Ezhil Ramya J¹¹, Nirmala Devi P¹¹, Anjali Bajaj^{1

2}, Vishu Gupta^{1

2}, Samatha Mathew^{1

2}, Sangam Goswami^{1

2}, Mohit Mangla^{1

2}, Savinitha Prakash¹, Kandarp Joshi¹, Meyakumla¹, Sreedevi S¹², Devarshi Gajjar¹³, Ronibala Soraisham¹⁴, Rohit Yadav^{1

2}, Yumnam Silla Devi¹⁵, Aayush Gupta¹⁶, Mitali Mukerji^{1

2}, Sivaprakash Ramalingam^{1

2}, Binukumar B K^{1

2}, Vinod Scaria^{17

18}, Sridhar Sivasubbu^{19

20}

Affiliations

¹ CSIR-Institute of Genomics and Integrative Biology, New Delhi, 110025, India.
² Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India.
³ Department of Zoology, RTM Nagpur University, Nagpur, Maharashtra, 440033, India.
⁴ Department of Zoology, Shri Mathuradas Mohota College of Science, Nagpur, Maharashtra, 440009, India.
⁵ Department of Anthropology, Vinoba Bhave University, Hazaribag, Jharkhand, 825301, India.
⁶ Department of Biotechnology, Vinoba Bhave University, Hazaribag, Jharkhand, 825301, India.
⁷ Department of Biochemistry, Dr. Kongu Science and Art College, Erode, Tamil Nadu, 638107, India.
⁸ Thalassemia and Sickle Cell Society, Hyderabad, Telangana, 500052, India.
⁹ Department of Biotechnology, Mizoram University, Aizawl, Mizoram, 796004, India.
¹⁰ Department of Pathology, Civil Hospital Aizawl, Mizoram, 796001, India.
¹¹ TVMC, Tirunelveli Medical College, Tirunelveli, Tamil Nadu, 627011, India.
¹² Department of Microbiology, St.Pious X Degree & PG College for Women, Hyderabad, Telangana, 500076, India.
¹³ Department of Microbiology, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390002, India.
¹⁴ Department of Dermatology, Venereology and Leprology, Regional Institute of Medical Sciences, Imphal, Manipur, 795004, India.
¹⁵ CSIR- North East Institute of Science and Technology, Jorhat, Assam, 785006, India.
¹⁶ Department of Dermatology, Dr. D.Y. Patil Medical College, Pune, Maharashtra, 411018, India.
¹⁷ CSIR-Institute of Genomics and Integrative Biology, New Delhi, 110025, India. vinods@igib.in.
¹⁸ Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India. vinods@igib.in.
¹⁹ CSIR-Institute of Genomics and Integrative Biology, New Delhi, 110025, India. sridhar@igib.in.
²⁰ Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India. sridhar@igib.in.

Abstract

Background: Autoinflammatory disorders are the group of inherited inflammatory disorders caused due to the genetic defect in the genes that regulates innate immune systems. These have been clinically characterized based on the duration and occurrence of unprovoked fever, skin rash, and patient's ancestry. There are several autoinflammatory disorders that are found to be prevalent in a specific population and whose disease genetic epidemiology within the population has been well understood. However, India has a limited number of genetic studies reported for autoinflammatory disorders till date. The whole genome sequencing and analysis of 1029 Indian individuals performed under the IndiGen project persuaded us to perform the genetic epidemiology of the autoinflammatory disorders in India.

Results: We have systematically annotated the genetic variants of 56 genes implicated in autoinflammatory disorder. These genetic variants were reclassified into five categories (i.e., pathogenic, likely pathogenic, benign, likely benign, and variant of uncertain significance (VUS)) according to the American College of Medical Genetics and Association of Molecular pathology (ACMG-AMP) guidelines. Our analysis revealed 20 pathogenic and likely pathogenic variants with significant differences in the allele frequency compared with the global population. We also found six causal founder variants in the IndiGen dataset belonging to different ancestry. We have performed haplotype prediction analysis for founder mutations haplotype that reveals the admixture of the South Asian population with other populations. The cumulative carrier frequency of the autoinflammatory disorder in India was found to be 3.5% which is much higher than reported.

Conclusion: With such frequency in the Indian population, there is a great need for awareness among clinicians as well as the general public regarding the autoinflammatory disorder. To the best of our knowledge, this is the first and most comprehensive population scale genetic epidemiological study being reported from India.

Keywords: Allele frequency; American College of Medical Genetics and Genomics; Autoinflammatory disorder; Genetic epidemiology; Haplotype ancestry.