alexa

GET THE APP

Replication And Prioritization Of Biological Pathways From Genome-wide Association Analysis Of Extreme Obesity | 6390
ISSN: 2165-7904

Journal of Obesity & Weight Loss Therapy
Open Access

Our Group organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations
700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

Replication and prioritization of biological pathways from genome-wide association analysis of extreme obesity

International Conference and Exhibition on Obesity & Weight Management

Sujoy Ghosh

ScientificTracks Abstracts: J Obes Wt Loss Ther

DOI: 10.4172/2165-7904.S1.002

Abstract
Pathway analysis addresses the missing heritability problem of SNP-centered GWAS data analysis by hypothesizing that a sufficient number of non-overlapping, non-concurrent disruptions in biological pathways, even with modest fractional contributions from single gene-variants, may be adequate to lead to a disorder. This approach is particularly relevant for disorders such as polygenic obesity where the contributions from individual SNP variants are typically quite low. However, a challenge faced by pathway analysis is that of replicating and prioritizing statistically associated pathways for downstream functional validation studies. To address this issue, we have developed a dual strategy of statistical replication and bioinformatic analysis, and applied this to identify and prioritize pathways based on GWA studies of extreme obesity. We employed 2 pathway analysis tools (iGSEA4GWAS and GSA-SNP) on an imputed ?Discovery? (985 cases/869 controls, BMI 43.1?8.7 and 20.3?1.84, respectively) and ?Replication? (540 cases/520 controls, BMI 49.4?8.8 and 20.7?1.8, respectively) cohort. Sixty-two (iGSEA4GWAS) and 22 (GSA-SNP) KEGG pathways from the Discovery cohort (p<0.05) were analyzed in the Replication cohort. A total of 19 pathways were replicated (p<0.05 level) between the 2 tools. The 19 replicated pathways were subsequently analyzed by the SNPNEXUS algorithm to calculate a ?SNP-burden? for each pathway, based on the estimated functional effects of the SNPs contained in them. A total of 16546 SNPs were analyzed. SNPs were scored for their location on chromosomal regions containing CPG islands, insertion-deletion regions, copy number polymorphisms, inversions, transcription factor binding sites, 3?- and 5?-UTRs, as well as amino-acid substitution effects on protein function. Finally, pathways were ranked by their predicted SNP-burden after normalization for the number of SNPs in each pathway. Two-way hierarchical clustering of pathway ranks and functional SNP categories identified the ?oxidative phosphorylation?, ?purine metabolism? and ?adipocytokine signaling? pathways as closely clustered with high SNP-burden across several functional categories. In conclusion, a combination of independent validation and bioinformatic analysis allows prioritization of GWAS pathway analysis to aid functional validation studies.
Biography
Top