1 Scientific RepoRts | 6:21440 | DOI: 10.1038/srep21440 www.nature.com/scientificreports Genome wide association study of uric acid in Indian population and interaction of identifed variants with Type 2 diabetes Anil K Giri 1,2 , priyanka Banerjee 1 , shraddha Chakraborty 1,2 , Yasmeen Kauser 1,2 , Aditya Undru 1,2 , suki Roy 1 , Vaisak parekatt 1 , Saurabh Ghosh 3 , Nikhil tandon 4 & Dwaipayan Bharadwaj 1,2,† Abnormal level of Serum Uric Acid (SUA) is an important marker and risk factor for complex diseases including Type 2 Diabetes. Since genetic determinant of uric acid in Indians is totally unexplored, we tried to identify common variants associated with SUA in Indians using Genome Wide Association Study (GWAS). Association of fve known variants in SLC2A9 and SLC22A11 genes with SUA level in 4,834 normoglycemics (1,109 in discovery and 3,725 in validation phase) was revealed with diferent efect size in Indians compared to other major ethnic population of the world. Combined analysis of 1,077 T2DM subjects (772 in discovery and 305 in validation phase) and normoglycemics revealed additional GWAS signal in ABCG2 gene. Diferences in efect sizes of ABCG2 and SLC2A9 gene variants were observed between normoglycemics and T2DM patients. We identifed two novel variants near long non-coding RNA genes AL356739.1 and AC064865.1 with nearly genome wide signifcance level. Meta-analysis and in silico replication in 11,745 individuals from AUSTWIN consortium improved association for rs12206002 in AL356739.1 gene to sub-genome wide association level. Our results extends association of SLC2A9, SLC22A11 and ABCG2 genes with SUA level in Indians and enrich the assemblages of evidence for SUA level and T2DM interrelationship. Uric acid is a by-product of oxidation of purine. SUA levels have been used as biological marker for many disor- ders like gout, arthritis, kidney functions 1,2 , hypertension, metabolic disorders and type 2 diabetes 3,4 . Studies have established SUA as an important stake holder regarding health issues of particular population. Hence it creates a necessity to study factors afecting SUA level of a population. Te levels of uric acid in an individual is a combined result of genetic factors and multitude of life style related factors like food habit, exercise, work type and means of transportation 5–8 . Indians difer in their food habit, living style and genetic constitutions from other ethnic populations in the world 9–11 . Genetic studies have established a heritability of 40–70% for SUA level suggesting stronger role of genetic factors in determining SUA level 12 . Major part of genetic factors contributing to the SUA level has not been well understood as few number of genetic studies have been performed in limited populations and most of them being of European ethnicity. GWAS conducted on Japanese, Chinese, African American and Amish populations have established association of loci in urate transporter genes like SLC2A9, ABCG2, SLC22A1 and SLC22A12 13–19 . Large scale meta-analysis conducted by Asian Genetic Epidemiology Network (AGEN) has included some sam- ples from the Singapore Indian Study (SINDI) and identifed loci in transcription factor MAF for SUA level 20 . Another large scale meta-analysis conducted by Global Urate Genetics Consortium 15 identifed 18 new loci asso- ciated with SUA level near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, 1 Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi - 110020, india. 2 Academy of Scientifc and Innovative Research, CSIR-Institute of Genomics and Integrative Biology Campus, New Delhi - 110020, India. 3 Human Genetics Unit, Indian Statistical Institute, Kolkata - 700108, India. 4 Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi - 110029, India. † Present address: School of Biotechnology, Jawaharlal Nehru University, New Delhi - 110067, India. Correspondence and requests for materials should be addressed to n. t. (email: nikhil_tandon@hotmail.com) or D.B. (email: db@mail.jnu.ac.in or db@jnu.ac.in) received: 12 October 2015 accepted: 22 January 2016 Published: 23 February 2016 OPEN