Document Detail

A resequence analysis of genomic loci on chromosomes 1q32.1, 5p15.33, and 13q22.1 associated with pancreatic cancer risk.
MedLine Citation:
PMID:  23295781     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: The objective of this study was to fine-map common pancreatic cancer susceptibility regions.
METHODS: We conducted targeted Roche-454 resequencing across 428 kb in 3 genomic regions identified in genome-wide association studies (GWAS) of pancreatic cancer, on chromosomes 1q32.1, 5p15.33, and 13q22.1.
RESULTS: An analytical pipeline for calling genotypes was developed using HapMap samples sequenced on chr5p15.33. Concordance to 1000 Genomes data for chr5p15.33 was greater than 96%. The concordance for chr1q32.1 and chr13q22.1 with pancreatic cancer GWAS data was greater than 99%. Between 9.2% and 19.0% of variants detected were not present in 1000 Genomes for the respective continental population. The majority of completely novel single-nucleotide polymorphisms (SNPs) were less common (minor allele frequency [MAF], ≤5%) or rare (MAF, ≤2%), illustrating the value of enlarging test sets for discovery of less common variants. Using the data set, we examined haplotype blocks across each region using a tag SNP analysis (r² > 0.8 for MAF of ≥5%) and determined that at least 196, 243, and 63 SNPs are required for fine-mapping chr1q32.1, chr5p15.33, and chr13q22.1, respectively, in European populations.
CONCLUSIONS: We have characterized germline variation in 3 regions associated with pancreatic cancer risk and show that targeted resequencing leads to the discovery of novel variants and improves the completeness of germline sequence variants for fine-mapping GWAS susceptibility loci.
Hemang Parikh; Jinping Jia; Xijun Zhang; Charles C Chung; Kevin B Jacobs; Meredith Yeager; Joseph Boland; Amy Hutchinson; Laura Burdett; Jason Hoskins; Harvey A Risch; Rachael Z Stolzenberg-Solomon; Stephen J Chanock; Brian M Wolpin; Gloria M Petersen; Charles S Fuchs; Patricia Hartge; Laufey Amundadottir
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  Pancreas     Volume:  42     ISSN:  1536-4828     ISO Abbreviation:  Pancreas     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-04-05     Completed Date:  2013-07-22     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  8608542     Medline TA:  Pancreas     Country:  United States    
Other Details:
Languages:  eng     Pagination:  209-15     Citation Subset:  IM    
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MeSH Terms
Chromosomes, Human, Pair 1*
Chromosomes, Human, Pair 13*
Chromosomes, Human, Pair 5*
Continental Population Groups / genetics
Databases, Genetic
Gene Frequency
Genetic Loci*
Genetic Predisposition to Disease
Genome-Wide Association Study
Linkage Disequilibrium
Pancreatic Neoplasms / ethnology,  genetics*
Polymorphism, Single Nucleotide*
Risk Assessment
Risk Factors
Sequence Analysis, DNA*
Grant Support
HHSN261200800001E//PHS HHS; K07 CA140790/CA/NCI NIH HHS; ZIA CP010193-05/CP/NCI NIH HHS

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