Genetic Architecture of Parkinson's Disease in the Indian Population: Harnessing Genetic Diversity to Address Critical Gaps in Parkinson's Disease Research

Roopa Rajan; K P Divya; Rukmini Mridula Kandadai; Ravi Yadav; Venkata P Satagopam; U K Madhusoodanan; Pankaj Agarwal; Niraj Kumar; Teresa Ferreira; Hrishikesh Kumar; A V Sreeram Prasad; Kuldeep Shetty; Sahil Mehta; Soaham Desai; Suresh Kumar; L K Prashanth; Mohit Bhatt; Pettarusp Wadia; Sudha Ramalingam; G M Wali; Sanjay Pandey; Felix Bartusch; Maximilian Hannussek; Jens Krüger; Ashwin Kumar-Sreelatha; Sandeep Grover; Peter Lichtner; Marc Sturm; Jochen Roeper; Volker Busskamp; Giriraj R Chandak; Jens Schwamborn; Pankaj Seth; Thomas Gasser; Olaf Riess; Vinay Goyal; Pramod Kumar Pal; Rupam Borgohain; Rejko Krüger; Asha Kishore; Manu Sharma; Lux-GIANT Consortium

doi:10.3389/fneur.2020.00524

Genetic Architecture of Parkinson's Disease in the Indian Population: Harnessing Genetic Diversity to Address Critical Gaps in Parkinson's Disease Research

Front Neurol. 2020 Jun 18:11:524. doi: 10.3389/fneur.2020.00524. eCollection 2020.

Authors

Roopa Rajan¹, K P Divya², Rukmini Mridula Kandadai³, Ravi Yadav⁴, Venkata P Satagopam^{5

6}, U K Madhusoodanan², Pankaj Agarwal⁷, Niraj Kumar⁸, Teresa Ferreira⁹, Hrishikesh Kumar¹⁰, A V Sreeram Prasad¹¹, Kuldeep Shetty¹², Sahil Mehta¹³, Soaham Desai¹⁴, Suresh Kumar¹⁵, L K Prashanth¹⁶, Mohit Bhatt¹⁷, Pettarusp Wadia¹⁸, Sudha Ramalingam¹⁹, G M Wali²⁰, Sanjay Pandey²¹, Felix Bartusch²², Maximilian Hannussek²², Jens Krüger²², Ashwin Kumar-Sreelatha²³, Sandeep Grover²³, Peter Lichtner²⁴, Marc Sturm²⁵, Jochen Roeper²⁶, Volker Busskamp²⁷, Giriraj R Chandak²⁸, Jens Schwamborn⁵, Pankaj Seth²⁹, Thomas Gasser³⁰, Olaf Riess²⁵, Vinay Goyal^{1

31}, Pramod Kumar Pal⁴, Rupam Borgohain³, Rejko Krüger^{5

32}, Asha Kishore², Manu Sharma²¹; Lux-GIANT Consortium

Affiliations

¹ Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
² Sree Chitra Tirunal Institute for Medical Sciences, Trivandrum, India.
³ Department of Neurology, Nizam's Institute of Medical Sciences, Hyderabad, India.
⁴ National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India.
⁵ Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Luxembourg, Luxembourg.
⁶ ELIXIR-Luxembourg Node, Belvaux, Luxembourg.
⁷ Movement Disorders Clinic, Global Hospitals, Mumbai, India.
⁸ All India Institute of Medical Sciences, Rishikesh, India.
⁹ Goa Medical College, Panaji, India.
¹⁰ Institute of Neurosciences, Kolkata, India.
¹¹ Lourdes Hospital, Kochi, India.
¹² Narayana Hrudayalaya Multispeciality Hospital, Bangalore, India.
¹³ Department of Neurology, PGIMER, Chandigarh, India.
¹⁴ Shree Krishna Hospital and Pramukhswami Medical College, Karamsad, India.
¹⁵ Department of Neurology, Vijaya Health Centre, Chennai, India.
¹⁶ Center for Parkinson's Disease and Movement Disorders, Vikram Hospital, Bangalore, India.
¹⁷ Kokilaben Dhirubhai Ambani Hospital, Mumbai, India.
¹⁸ Jaslok Hospital, Mumbai, India.
¹⁹ Department of Community Medicine, PSG Institute of Medical Sciences and Research, Coimbatore, India.
²⁰ Neurospecialities Centre, Belgaum, India.
²¹ Department of Neurology, G. B. Pant Institute of Medical Education and Research, New Delhi, India.
²² Zentrum für Datenverarbeitung (ZDV), University of Tubingen, Tübingen, Germany.
²³ Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Tübingen, Germany.
²⁴ Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Human Genetics, Neuherberg, Germany.
²⁵ Institute for Medical Genetics and Applied Genomics, University of Tubingen, Tübingen, Germany.
²⁶ Institute of Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany.
²⁷ Department of Ophthalmology, Universitäts-Augenklinik Bonn, University of Bonn, Bonn, Germany.
²⁸ Centre for Cellular and Molecular Biology, Hyderabad, India.
²⁹ National Brain Research Centre, Gurugram, India.
³⁰ Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
³¹ Medanta the Medicity, Gurgaon, India.
³² Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Strassen, Luxembourg.

Abstract

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our "hub-spoke" model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD.

Keywords: Parkinson's disease; biobank; common genetic variation; genetic diversity; genome-wide association study.

Copyright © 2020 Rajan, Divya, Kandadai, Yadav, Satagopam, Madhusoodanan, Agarwal, Kumar, Ferreira, Kumar, Sreeram Prasad, Shetty, Mehta, Desai, Kumar, Prashanth, Bhatt, Wadia, Ramalingam, Wali, Pandey, Bartusch, Hannussek, Krüger, Kumar-Sreelatha, Grover, Lichtner, Sturm, Roeper, Busskamp, Chandak, Schwamborn, Seth, Gasser, Riess, Goyal, Pal, Borgohain, Krüger, Kishore, Sharma and the Lux-GIANT Consortium.