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Best practices and joint calling of the HumanExome BeadChip: the CHARGE Consortium.

TitleBest practices and joint calling of the HumanExome BeadChip: the CHARGE Consortium.
Publication TypeJournal Article
Year of Publication2013
AuthorsGrove, ML, Yu, B, Cochran, BJ, Haritunians, T, Bis, JC, Taylor, KD, Hansen, M, Borecki, IB, Cupples, AL, Fornage, M, Gudnason, V, Harris, TB, Kathiresan, S, Kraaij, R, Launer, LJ, Levy, D, Liu, Y, Mosley, T, Peloso, GM, Psaty, BM, Rich, SS, Rivadeneira, F, Siscovick, DS, Smith, AV, Uitterlinden, A, van Duijn, CM, Wilson, JG, O'Donnell, CJ, Rotter, JI, Boerwinkle, E
JournalPLoS One
Volume8
Issue7
Paginatione68095
Date Published2013
ISSN1932-6203
KeywordsAging, Alleles, Cluster Analysis, Cohort Studies, Continental Population Groups, Exome, Female, Gene Frequency, Genomics, Genotype, Heart, Humans, Male, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Sample Size, Self Report, Sequence Analysis, DNA
Abstract<p>Genotyping arrays are a cost effective approach when typing previously-identified genetic polymorphisms in large numbers of samples. One limitation of genotyping arrays with rare variants (e.g., minor allele frequency [MAF] <0.01) is the difficulty that automated clustering algorithms have to accurately detect and assign genotype calls. Combining intensity data from large numbers of samples may increase the ability to accurately call the genotypes of rare variants. Approximately 62,000 ethnically diverse samples from eleven Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium cohorts were genotyped with the Illumina HumanExome BeadChip across seven genotyping centers. The raw data files for the samples were assembled into a single project for joint calling. To assess the quality of the joint calling, concordance of genotypes in a subset of individuals having both exome chip and exome sequence data was analyzed. After exclusion of low performing SNPs on the exome chip and non-overlap of SNPs derived from sequence data, genotypes of 185,119 variants (11,356 were monomorphic) were compared in 530 individuals that had whole exome sequence data. A total of 98,113,070 pairs of genotypes were tested and 99.77% were concordant, 0.14% had missing data, and 0.09% were discordant. We report that joint calling allows the ability to accurately genotype rare variation using array technology when large sample sizes are available and best practices are followed. The cluster file from this experiment is available at www.chargeconsortium.com/main/exomechip. </p>
DOI10.1371/journal.pone.0068095
Alternate JournalPLoS ONE
PubMed ID23874508
PubMed Central IDPMC3709915
Grant ListN01-HC-25195 / HC / NHLBI NIH HHS / United States
U01 HL56565 / HL / NHLBI NIH HHS / United States
N01-HC-45205 / HC / NHLBI NIH HHS / United States
R01-HL-071258, , / HL / NHLBI NIH HHS / United States
N01-HC-95162 / HC / NHLBI NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
N01-HC-05187 / HC / NHLBI NIH HHS / United States
R01-HL-071252 / HL / NHLBI NIH HHS / United States
5RC2HL102419 / HL / NHLBI NIH HHS / United States
N01 HC-95171 / HC / NHLBI NIH HHS / United States
U01 HL56564 / HL / NHLBI NIH HHS / United States
HHSN2682011000010C / / PHS HHS / United States
UL1-RR-025005 / RR / NCRR NIH HHS / United States
N01-HC-48047 / HC / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
N01AG62101 / AG / NIA NIH HHS / United States
N01-HC-95163 / HC / NHLBI NIH HHS / United States
R01-HL-071250 / HL / NHLBI NIH HHS / United States
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AG-15928 / AG / NIA NIH HHS / United States
U01 HL56566 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
N01-HC-45204 / HC / NHLBI NIH HHS / United States
N01-HC-95159 / HC / NHLBI NIH HHS / United States
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DK-35816 / DK / NIDDK NIH HHS / United States
N01-HC-95095 / HC / NHLBI NIH HHS / United States
N01-HC-95165 / HC / NHLBI NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
U01 HL56569 / HL / NHLBI NIH HHS / United States
R01-HL-071251 / HL / NHLBI NIH HHS / United States
R01-HL-084099 / HL / NHLBI NIH HHS / United States
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