<i>EGLN1</i> involvement in high-altitude adaptation revealed through genetic analysis of extreme constitution types defined in Ayurveda
Shilpi Aggarwal(Institute of Genomics and Integrative Biology), Sapna Negi(Institute of Genomics and Integrative Biology), Pankaj Jha(Institute of Genomics and Integrative Biology), Prashant Kumar Singh(Institute of Genomics and Integrative Biology), Tsering Stobdan(Institute of Genomics and Integrative Biology), M. A. Qadar Pasha(Institute of Genomics and Integrative Biology), Saurabh Ghosh(Indian Statistical Institute), Anurag Agrawal(Institute of Genomics and Integrative Biology), Bhavana Prasher(Institute of Genomics and Integrative Biology), Mitali Mukerji(Indian Institute of Technology Jodhpur), Samir K. Brahmachari, Partha P. Majumder, Mitali Mukerji(Indian Institute of Technology Jodhpur), Saman Habib(Institute of Genomics and Integrative Biology), Debasis Dash, Kunal Ray(Indian Institute of Technology Jodhpur), S. Bahl(Institute of Genomics and Integrative Biology), Lalji Singh(Institute of Genomics and Integrative Biology), Abhay Sharma, Susanta Roychoudhury(Institute of Genomics and Integrative Biology), Giriraj R. Chandak(Institute of Genomics and Integrative Biology), Kumarasamy Thangaraj(Indian Institute of Technology Jodhpur), Devendra Parmar, Shiladitya Sengupta(Institute of Genomics and Integrative Biology), Dwaipayan Bharadwaj, Srikanta Kumar Rath, J. Singh(Institute of Genomics and Integrative Biology), Ganga Nath Jha(Institute of Genomics and Integrative Biology), Komal Virdi(Indian Institute of Technology Jodhpur), Vadlamudi Raghavendra Rao, Swapnil Sinha(Institute of Genomics and Integrative Biology), Ashish Kumar Singh(Institute of Genomics and Integrative Biology), Amit Mitra(Indian Institute of Technology Jodhpur), Shrawan K. Mishra, Qadar Pasha(Institute of Genomics and Integrative Biology), Sridhar Sivasubbu(Institute of Genomics and Integrative Biology), Rajesh Pandey(Indian Institute of Technology Jodhpur), Aradhita Baral, P. K. Singh(Institute of Genomics and Integrative Biology), Abhay Sharma, Jitender Kumar(Indian Institute of Technology Jodhpur), Tsering Stobdan(Institute of Genomics and Integrative Biology), Yasha Bhasin, C Chauhan, Ashik Hussain, Elayanambi Sundaramoorthy(Indian Institute of Technology Jodhpur), SP Singh(Institute of Genomics and Integrative Biology), Arun Bandyopadhyay, Kamal Dasgupta(Indian Institute of Technology Jodhpur), A. K. Reddy(Indian Institute of Technology Jodhpur), Charles J. Spurgeon, Mohammed M. Idris, Vinay K. Khanna(Institute of Genomics and Integrative Biology), Uma Dhawan, M. Anand(Indian Institute of Technology Jodhpur), Ravi Shankar(Indian Institute of Technology Jodhpur), Ram Suresh Bharti, Mahendra Pratap Singh(Institute of Genomics and Integrative Biology), Ashish Pratap Singh(Institute of Genomics and Integrative Biology), Anwar Jamal Khan(Indian Institute of Technology Jodhpur), Parag P. Shah, AB Pant(Institute of Genomics and Integrative Biology), Rupinder Kaur(Indian Institute of Technology Jodhpur), Kamlesh Bisht, A. Kumar, V. Rajamanickam(Institute of Genomics and Integrative Biology), Elizabeth Wilson(Indian Institute of Technology Jodhpur), Antony Thangadurai, Pankaj Jha(Institute of Genomics and Integrative Biology), Mahua Maulik(Indian Institute of Technology Jodhpur), Namrata Kumar Makhija(Institute of Genomics and Integrative Biology), Abdur Rahim, Surendra K. Sharma(Institute of Genomics and Integrative Biology), Rupali Chopra(Indian Institute of Technology Jodhpur), Palak Rana(Institute of Genomics and Integrative Biology), Manickam Chidambaram(Indian Institute of Technology Jodhpur), Arindam Maitra, Ruchi Chawla(Indian Institute of Technology Jodhpur), Shivani Soni(Institute of Genomics and Integrative Biology), Preeti Khurana(Institute of Genomics and Integrative Biology), M. Nadeem Khan, Sushanta Das Sutar, Amit Tuteja, K. Narayansamy(Indian Institute of Technology Jodhpur), Rammohan Shukla(Indian Institute of Technology Jodhpur), Satya Prakash(Institute of Genomics and Integrative Biology), Swapna Mahurkar‐Joshi(Institute of Genomics and Integrative Biology), K. Radha Mani, J. Hemavathi(Indian Institute of Technology Jodhpur), S. Bhaskar(Institute of Genomics and Integrative Biology), Pankaj Khanna(Institute of Genomics and Integrative Biology), G. S. Ramalakshmi(Institute of Genomics and Integrative Biology), S. M. Tripathi, Neelam Thakur(Institute of Genomics and Integrative Biology), B. Ghosh(Indian Statistical Institute), Ritushree Kukreti(Indian Institute of Technology Jodhpur), Taruna Madan(Indian Institute of Technology Jodhpur), Rajesh Verma(Indian Institute of Technology Jodhpur), G. Sudheer, Anubha Mahajan, Sreenivas Chavali(Institute of Genomics and Integrative Biology), Rubina Tabassum(Indian Institute of Technology Jodhpur), Sandeep Grover(Institute of Genomics and Integrative Biology), Meenal Gupta(Indian Institute of Technology Jodhpur), Jyotsna Batra(Indian Institute of Technology Jodhpur), A. Kumar, Azim Nejatizadeh, Mudit Vaid(Indian Institute of Technology Jodhpur), Suman Das, Suresh C. Sharma(Institute of Genomics and Integrative Biology), Manu Sharma(Indian Institute of Technology Jodhpur), Rajshekhar Chatterjee(Indian Institute of Technology Jodhpur), Jinny Paul(Indian Institute of Technology Jodhpur), Pragya Srivastava(Institute of Genomics and Integrative Biology), Charu Rajput, Uma Mittal(Indian Institute of Technology Jodhpur), Mahendra Pratap Singh(Institute of Genomics and Integrative Biology), M. Hariharan(Indian Institute of Technology Jodhpur), Sumit Das(Institute of Genomics and Integrative Biology), К. Ray Chaudhuri(Indian Institute of Technology Jodhpur), Mainak Sengupta(Indian Institute of Technology Jodhpur), Moulinath Acharya(Indian Institute of Technology Jodhpur), Anirban Bhattacharyya, Atreyee Saha, Arindam Biswas, Moumita Chaki(Indian Institute of Technology Jodhpur), Arnab Gupta, Somnath Mukherjee(Institute of Genomics and Integrative Biology), Suddhasil Mookherjee(Institute of Genomics and Integrative Biology), Ishita Chattopadhyay(Indian Institute of Technology Jodhpur), Tapas Kumar Banerjee(Indian Institute of Technology Jodhpur), Meenakshi Chakravorty(Indian Institute of Technology Jodhpur), Chaitali Misra, Gourish Monadal, Shiladitya Sengupta(Institute of Genomics and Integrative Biology), De. D. Dutta, Swati Bajaj(Institute of Genomics and Integrative Biology), Ishani Deb(Indian Institute of Technology Jodhpur), Saumyabrata Banerjee, Rajdeep Chowdhury(Indian Institute of Technology Jodhpur), Deblina Banerjee, Dhirendra Kumar, Sumit Das, Shrish Tiwari(Institute of Genomics and Integrative Biology), Anshu Bharadwaj, Shweta Khanna(Institute of Genomics and Integrative Biology), Ikhlak Ahmed(Indian Institute of Technology Jodhpur), Shaista Parveen(Institute of Genomics and Integrative Biology), Nivedita Singh(Institute of Genomics and Integrative Biology), D. Dasgupta, Siddharth Singh Bisht, Rahul Singh Rajput(Indian Institute of Technology Jodhpur), B. Ghosh(Indian Statistical Institute), Neeraj Kumar(Institute of Genomics and Integrative Biology), Amit Chaurasia, J.K. Abraham, Amit Kumar Sinha, Vinod Scaria(Institute of Genomics and Integrative Biology), Tavpritesh Sethi, Amit Kumar Mandal(Indian Institute of Technology Jodhpur), Arijit Mukhopadhyay
Cited by 170Open Access
Abstract
It is being realized that identification of subgroups within normal controls corresponding to contrasting disease susceptibility is likely to lead to more effective predictive marker discovery. We have previously used the Ayurvedic concept of Prakriti, which relates to phenotypic differences in normal individuals, including response to external environment as well as susceptibility to diseases, to explore molecular differences between three contrasting Prakriti types: Vata, Pitta, and Kapha. EGLN1 was one among 251 differentially expressed genes between the Prakriti types. In the present study, we report a link between high-altitude adaptation and common variations rs479200 (C/T) and rs480902 (T/C) in the EGLN1 gene. Furthermore, the TT genotype of rs479200, which was more frequent in Kapha types and correlated with higher expression of EGLN1, was associated with patients suffering from high-altitude pulmonary edema, whereas it was present at a significantly lower frequency in Pitta and nearly absent in natives of high altitude. Analysis of Human Genome Diversity Panel-Centre d'Etude du Polymorphisme Humain (HGDP-CEPH) and Indian Genome Variation Consortium panels showed that disparate genetic lineages at high altitudes share the same ancestral allele (T) of rs480902 that is overrepresented in Pitta and positively correlated with altitude globally (P < 0.001), including in India. Thus, EGLN1 polymorphisms are associated with high-altitude adaptation, and a genotype rare in highlanders but overrepresented in a subgroup of normal lowlanders discernable by Ayurveda may confer increased risk for high-altitude pulmonary edema.