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Dive into the research topics where Dwaipayan Bharadwaj is active.

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Featured researches published by Dwaipayan Bharadwaj.


PLOS ONE | 2012

Genetic Variant of AMD1 Is Associated with Obesity in Urban Indian Children

Rubina Tabassum; Alok Jaiswal; Ganesh Chauhan; Om Prakash Dwivedi; Saurabh Ghosh; Raman K. Marwaha; Nikhil Tandon; Dwaipayan Bharadwaj

Background Hyperhomocysteinemia is regarded as a risk factor for cardiovascular diseases, diabetes and obesity. Manifestation of these chronic metabolic disorders starts in early life marked by increase in body mass index (BMI). We hypothesized that perturbations in homocysteine metabolism in early life could be a link between childhood obesity and adult metabolic disorders. Thus here we investigated association of common variants from homocysteine metabolism pathway genes with obesity in 3,168 urban Indian children. Methodology/Principal Findings We genotyped 90 common variants from 18 genes in 1,325 children comprising of 862 normal-weight (NW) and 463 over-weight/obese (OW/OB) children in stage 1. The top signal obtained was replicated in an independent sample set of 1843 children (1,399 NW and 444 OW/OB) in stage 2. Stage 1 association analysis revealed association between seven variants and childhood obesity at P<0.05, but association of only rs2796749 in AMD1 [ORu200a=u200a1.41, Pu200a=u200a1.5×10-4] remained significant after multiple testing correction. Association of rs2796749 with childhood obesity was validated in stage 2 [ORu200a=u200a1.28, Pu200a=u200a4.2×10-3] and meta-analysis [ORu200a=u200a1.35, Pu200a=u200a1.9×10-6]. AMD1 variant rs2796749 was also associated with quantitative measures of adiposity and plasma leptin levels that was also replicated and corroborated in combined analysis. Conclusions/Significance Our study provides first evidence for the association of AMD1 variant with obesity and plasma leptin levels in children. Further studies to confirm this association, its functional significance and mechanism of action need to be undertaken.


PLOS ONE | 2012

Common Variants of FTO Are Associated with Childhood Obesity in a Cross-Sectional Study of 3,126 Urban Indian Children

Om Prakash Dwivedi; Rubina Tabassum; Ganesh Chauhan; Saurabh Ghosh; Raman K. Marwaha; Nikhil Tandon; Dwaipayan Bharadwaj

Background FTO variants are robustly associated with obesity and related traits in many population and shown to have variable impact during life course. Although studies have shown association of FTO variants with adiposity in adult Indian, its association in Indian children is yet to be confirmed. Methods Here we examined association of FTO variants (rs9939609 and rs8050136) with obesity and related anthropometric and biochemical traits in 3,126 Indian children (aged 11–17 years) including 2,230 normal-weight and 896 over-weight/obese children. We also compared effects observed in the present study with that observed in previous studies on South Asian adults and children of other ethnic groups. Results The variant rs9939609 showed significant association with risk of obesity [ORu200a=u200a1.21, Pu200a=u200a2.5×10−3] and its measures BMI, weight, waist circumference and hip circumference [β rangeu200a=u200a0.11 to 0.14 Z-score units; P rangeu200a=u200a1.3×10−4 to 1.6×10−7] in children. The observed effect sizes in Indian children were similar to those reported for European children. Variant rs9939609 explained 0.88% of BMI variance in Indian children. The effect sizes of rs9939609 on BMI and WC were ∼2 fold higher in children than adults. Interestingly rs9939609 was also associated with serum levels of thyroid stimulating hormone (TSH) [βu200a=u200a0.10 Z-score, Pu200a=u200a5.8×10−3]. The other variant rs8050136 was in strong linkage disequilibrium with rs9939609 (r2u200a=u200a0.97) and provided similar association results. Conclusion The study provides first report of association of FTO variants with obesity and related anthropometric traits in Indian children with higher impact in children compared to adults. We also demonstrated association of FTO variant with serum levels of TSH, indicating putative influence of FTO in hypothalamic-pituitary-thyroid axis.


Atherosclerosis | 2012

Elevated level of C-reactive protein is associated with risk of prediabetes in Indians

Alok Jaiswal; Rubina Tabassum; Avijit Podder; Saurabh Ghosh; Nikhil Tandon; Dwaipayan Bharadwaj

BACKGROUNDnRelationship of high sensitivity C-reactive protein (hsCRP) with prediabetes has not been explored extensively in Indians. Here we sought to investigate the association of hsCRP levels with prediabetes, as represented by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and the influence of risk factors like obesity, decreased HDL cholesterol, hypertension, family history of diabetes and current smoking habit on the relationship.nnnMETHODSnA cross-sectional study on 1726 Indians, comprising of 1276 individuals with normal glucose tolerance (NGT), 250 IFG and 200 IGT individuals. Subjects were defined according to WHO criteria based on fasting plasma and 2 h glucose levels.nnnRESULTSnMedian levels of hsCRP were significantly higher in IFG (2.20 mg/l) and IGT (2.32 mg/l) compared to NGT (1.64 mg/l) subjects. Individuals with high risk hsCRP levels (>3 mg/l) had an odds ratio (OR) (95% confidence interval (CI)) of 2.60 (1.56-5.34) [P=1.3×10(-4)] for IGT after adjusting the effect of age, sex, medication, body mass index (BMI), waist circumference (WC) and risk factors like decreased high-density lipoprotein cholesterol (HDL-cholesterol), hypertension, family history of diabetes and current smoking. Significant increase in risk of IGT was found with a unit increase in natural log transformed hsCRP levels after adjustment for covariates [OR (95%CI)=1.57 (1.27-1.94), P=3.0×10(-5)]. When subjects were stratified on the basis of risk factors, we found stronger association of elevated hsCRP levels with risk of IFG and IGT in subjects having HDL-cholesterol ≤50 mg/dl and with hypertension.nnnCONCLUSIONSnOur study demonstrates that elevated hsCRP levels are independently associated with risk of IFG and IGT in Indians.


PLOS ONE | 2016

Common Variants in CLDN2 and MORC4 Genes Confer Disease Susceptibility in Patients with Chronic Pancreatitis.

Anil K. Giri; Shallu Midha; Priyanka Banerjee; Ankita Agrawal; Syed Jafar Mehdi; Rajan Dhingra; Ismeet Kaur; G Ramesh Kumar; Ritika Lakhotia; Saurabh Ghosh; Kshaunish Das; Samir Mohindra; Surinder S. Rana; Deepak K. Bhasin; Pramod Kumar Garg; Dwaipayan Bharadwaj; Indipan

A recent genome-wide association study (GWAS) identified association with variants in X-linked CLDN2 and MORC4, and PRSS1-PRSS2 loci with chronic pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525—OR 1.71, P = 1.38 x 10-09; rs12008279—OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220—OR 1.72, P = 9.20 x 10-09; rs6622126—OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31–0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients.


PLOS ONE | 2011

Common variants in CRP and LEPR influence high sensitivity C-reactive protein levels in north Indians

Anubha Mahajan; Rubina Tabassum; Sreenivas Chavali; Om Prakash Dwivedi; Ganesh Chauhan; Saurabh Ghosh; Nikhil Tandon; Dwaipayan Bharadwaj

Background High sensitivity C-reactive protein (hsCRP) levels are shown to be influenced by genetic variants in Europeans; however, little is explored in Indian population. Methods Herein, we comprehensively evaluated association of all previously reported genetic determinants of hsCRP levels, including 18 cis (proximal to CRP gene) and 73 trans-acting (distal to CRP gene) variants in 4,200 North Indians of Indo-European ethnicity. First, we evaluated association of 91 variants from 12 candidate loci with hsCRP levels in 2,115 North Indians (1,042 non-diabetic subjects and 1,073 patients with type 2 diabetes). Then, cis and trans-acting variants contributing maximally to hsCRP level variation were further replicated in an independent 2,085 North Indians (1,047 patients with type 2 diabetes and 1,038 non-diabetic subjects). Results We found association of 12 variants from CRP, LEPR, IL1A, IL6, and IL6R with hsCRP levels in non-diabetic subjects. However, only rs3093059-CRP [βu200a=u200a0.33, Pu200a=u200a9.6×10−5] and the haplotype harboring rs3093059 risk allele [βu200a=u200a0.32 µg/mL, Pu200a=u200a1.4×10−4/Ppermu200a=u200a9.0×10−4] retained significance after correcting for multiple testing. The cis-acting variant rs3093059-CRP had maximum contribution to the variance in hsCRP levels (1.14%). Among, trans-acting variants, rs1892534-LEPR was observed to contribute maximally to hsCRP level variance (0.59%). Associations of rs3093059-CRP and rs1892534-LEPR were confirmed by replication and attained higher significance after meta-analysis [βmetau200a=u200a0.26/0.22; Pmetau200a=u200a4.3×10−7/7.4×10−3 and βmetau200a=u200a−0.15/−0.12; Pmetau200a=u200a2.0×10−6/1.6×10−6 for rs3093059 and rs1892534, respectively in non-diabetic subjects and all subjects taken together]. Conclusion In conclusion, we identified rs3093059 in CRP and rs1892534 in LEPR as major cis and trans-acting contributor respectively, to the variance in hsCRP levels in North Indian population.


BMC Medical Genetics | 2011

No association of TNFRSF1B variants with type 2 diabetes in Indians of Indo-European origin

Rubina Tabassum; Anubha Mahajan; Ganesh Chauhan; Om Prakash Dwivedi; Himanshu Dubey; Vasudha Sharma; Bratashree Kundu; Saurabh Ghosh; Nikhil Tandon; Dwaipayan Bharadwaj

BackgroundThere has been no systematic evaluation of the association between genetic variants of type 2 receptor for TNFα (TNFR2) and type 2 diabetes, despite strong biological evidence for the role of this receptor in the pathogenesis of this complex disorder. In view of this, we performed a comprehensive association analysis of TNFRSF1B variants with type 2 diabetes in 4,200 Indo-European subjects from North India.MethodsThe initial phase evaluated association of seven SNPs viz. rs652625, rs496888, rs6697733, rs945439, rs235249, rs17883432 and rs17884213 with type 2 diabetes in 2,115 participants (1,073 type 2 diabetes patients and 1,042 control subjects). Further, we conducted replication analysis of three associated SNPs in 2,085 subjects (1,047 type 2 diabetes patients and 1,038 control subjects).ResultsWe observed nominal association of rs945439, rs235249 and rs17884213 with type 2 diabetes (P < 0.05) in the initial phase. Haplotype CC of rs945439 and rs235249 conferred increased susceptibility for type 2 diabetes [OR = 1.19 (95%CI 1.03-1.37), P = 0.019/Pperm = 0.076] whereas, TG haplotype of rs235249 and rs17884213 provided protection against type 2 diabetes [OR = 0.83 (95%CI 0.72-0.95, P = 7.2 × 10-3/Pperm = 0.019]. We also observed suggestive association of rs496888 with plasma hsCRP levels [P = 0.042]. However, the association of rs945439, rs235249 and rs17884213 with type 2 diabetes was not replicated in the second study population. Meta-analysis of the two studies also failed to detect any association with type 2 diabetes.ConclusionsOur two-stage association analysis suggests that TNFRSF1B variants are not the determinants of genetic risk of type 2 diabetes in North Indians.


Molecular Genetics and Genomics | 2017

DNA methylation profiling reveals the presence of population-specific signatures correlating with phenotypic characteristics

Anil K. Giri; Soham Bharadwaj; Priyanka Banerjee; Shraddha Chakraborty; Vaisak Parekatt; Donaka Rajashekar; Abhishek Tomar; Aarthi Ravindran; Analabha Basu; Nikhil Tandon; Dwaipayan Bharadwaj

Phenotypic characteristics are known to vary substantially among different ethnicities around the globe. These variations are mediated by number of stochastic events and cannot be attributed to genetic architecture alone. DNA methylation is a well-established mechanism that sculpts our epigenome influencing phenotypic variation including disease manifestation. Since DNA methylation is an important determinant for health issues of a population, it demands a thorough investigation of the natural differences in genome wide DNA methylation patterns across different ethnic groups. This study is based on comparative analyses of methylome from five different ethnicities with major focus on Indian subjects. The current study uses hierarchical clustering approaches, principal component analysis and locus specific differential methylation analysis on Illumina 450K methylation data to compare methylome of different ethnic subjects. Our data indicates that the variations in DNA methylation patterns of Indians are less among themselves compared to other global population. It empirically correlated with dietary, cultural and demographical divergences across different ethnic groups. Our work further suggests that Indians included in this study, despite their genetic similarity with the Caucasian population, are in close proximity with Japanese in terms of their methylation signatures.


Scientific Reports | 2018

Common variants of ARID1A and KAT2B are associated with obesity in Indian adolescents

Anil K. Giri; Vaisak Parekatt; Om Prakash Dwivedi; Priyanka Banerjee; Khushdeep Bandesh; Gauri Prasad; Nikhil Tandon; Dwaipayan Bharadwaj

Obesity involves alterations in transcriptional programs that can change in response to genetic and environmental signals through chromatin modifications. Since chromatin modifications involve different biochemical, neurological and molecular signaling pathways related to energy homeostasis, we hypothesize that genetic variations in chromatin modifier genes can predispose to obesity. Here, we assessed the associations between 179 variants in 35 chromatin modifier genes and overweight/obesity in 1283 adolescents (830 normal weight and 453 overweight/obese). This was followed up by the replication analysis of associated signals (18 variants in 8 genes) in 2247 adolescents (1709 normal weight and 538 overweight/obese). Our study revealed significant associations of two variants rs6598860 (ORu2009=u20091.27, Pu2009=u20091.58u2009×u200910–4) and rs4589135 (ORu2009=u20091.22, Pu2009=u20093.72u2009×u200910–4) in ARID1A with overweight/obesity. We also identified association of rs3804562 (βu2009=u20090.11, Pu2009=u20091.35u2009×u200910–4) in KAT2B gene with BMI. In conclusion, our study suggests a potential role of ARID1A and KAT2B genes in the development of obesity in adolescents and provides leads for further investigations.


Pharmacogenomics | 2018

Pharmacogenetic landscape of DPYD variants in south Asian populations by integration of genome-scale data.

Judith Mary Hariprakash; Shamsudheen Karuthedath Vellarikkal; Pavithran Keechilat; Ankit Verma; Rijith Jayarajan; Vishal Dixit; Rowmika Ravi; Vigneshwar Senthivel; Anoop Kumar; Paras Sehgal; Akhilesh K Sonakar; Sakshi Ambawat; Anil K. Giri; Arun Philip; Akhila Sivadas; Mohammed Faruq; Dwaipayan Bharadwaj; Sridhar Sivasubbu; Vinod Scaria

AIMnAdverse drug reactions to 5-Fluorouracil(5-FU) is frequent and largely attributable to genetic variations in the DPYD gene, a rate limiting enzyme that clears 5-FU. The study aims at understanding the pharmacogenetic landscape of DPYD variants in south Asian populations.nnnMATERIALS & METHODSnSystematic analysis of population scale genome wide datasets of over 3000 south Asians was performed. Independent evaluation was performed in a small cohort of patients.nnnRESULTSnOur analysis revealed significant differences in the the allelic distribution of variants in different ethnicities.nnnCONCLUSIONSnThis is the first and largest genetic map the DPYD variants associated with adverse drug reaction to 5-FU in south Asian population. Our study highlights ethnic differences in allelic frequencies.


Archive | 2018

A Systems Perspective of Complex Diseases: From Reductionism to Integration

Khushdeep Bandesh; Pawan K. Dhar; Dwaipayan Bharadwaj

Complex systems exist across all levels of biological organization ranging from the simplest (subatomic realm) to most complex (individual organism to whole populations and beyond). This complex nature of both the common diseases and the human beings has kept researchers far from a holistic understanding of underlying biological processes. Over the past decade, there has been a rapid and vast accumulation of large scale high-throughput biological data at physiological, cellular, molecular, and submolecular levels. It includes genetic association studies of complex human diseases and traits, quantification of genome-wide RNA expression patterns, comprehensive profiling of cellular proteins and metabolites, gene regulatory information (DNA methylation, histone modifications, chromatin accessibility, evolutionary constraint, etc.), and characterization of networks of molecular interactions. The clinical utility of such enormous data demands interpretation and understanding at the biological level to reveal mechanistic insights of molecular etiology. An important element of this task is to complement the detailed pieces of biological information with new advanced methods of system integration and reconstruction. This requires conversion of actual biological systems into computational models to make reliable predictions of biological responses following targeted manipulation under untested conditions. The frequency at which signals are presently being discovered mandates a systematic and integrative “omics” approach to bridge the “genotype to phenotype” gap. The chapter highlights the fundamental ways to integrate high-quality biological data that await systemic interpretations.

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Nikhil Tandon

All India Institute of Medical Sciences

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Saurabh Ghosh

Indian Statistical Institute

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Anil K. Giri

Institute of Genomics and Integrative Biology

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Om Prakash Dwivedi

Institute of Genomics and Integrative Biology

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Rubina Tabassum

Institute of Genomics and Integrative Biology

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Ganesh Chauhan

Institute of Genomics and Integrative Biology

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Priyanka Banerjee

Institute of Genomics and Integrative Biology

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Alok Jaiswal

Institute of Genomics and Integrative Biology

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Anubha Mahajan

Institute of Genomics and Integrative Biology

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Ismeet Kaur

Institute of Genomics and Integrative Biology

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