Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/98803
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Type: Journal article
Title: Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on Body Mass Index
Author: Hoggart, C.
Venturini, G.
Mangino, M.
Gomez, F.
Ascari, G.
Zhao, J.
Teumer, A.
Winkler, T.
Tšernikova, N.
Luan, J.
Mihailov, E.
Ehret, G.
Zhang, W.
Lamparter, D.
Esko, T.
Macé, A.
Rüeger, S.
Bochud, P.
Barcella, M.
Dauvilliers, Y.
et al.
Citation: PLoS Genetics, 2014; 10(7):e1004508-1-e1004508-12
Publisher: Public Library of Science
Issue Date: 2014
ISSN: 1553-7404
1553-7404
Statement of
Responsibility: 
Clive J. Hoggart ... Generation Scotland Consortium ... The LifeLines Cohort study ... The GIANT Consortium ... et al. Lyle J. Palmer is a member of the Genetic Investigation of ANthropometric Traits (GIANT) Consortium
Abstract: The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to .56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ,4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P,0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P,0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.
Keywords: Generation Scotland Consortium; LifeLines Cohort study; GIANT Consortium; Humans; Obesity; Genetic Predisposition to Disease; Potassium Channels, Tandem Pore Domain; Body Mass Index; Gene Expression Regulation; Genomic Imprinting; Genotype; Polymorphism, Single Nucleotide; Adult; European Continental Ancestry Group; Female; Male; Glucose Transport Proteins, Facilitative; Genome-Wide Association Study
Rights: © 2014 Hoggart et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030032676
DOI: 10.1371/journal.pgen.1004508
Grant ID: http://purl.org/au-research/grants/nhmrc/241944
http://purl.org/au-research/grants/nhmrc/389875
http://purl.org/au-research/grants/nhmrc/389891
http://purl.org/au-research/grants/nhmrc/389892
http://purl.org/au-research/grants/nhmrc/389938
http://purl.org/au-research/grants/nhmrc/442915
http://purl.org/au-research/grants/nhmrc/442981
http://purl.org/au-research/grants/nhmrc/496739
http://purl.org/au-research/grants/nhmrc/496688
http://purl.org/au-research/grants/nhmrc/552485
http://purl.org/au-research/grants/nhmrc/613672
http://purl.org/au-research/grants/arc/DP0770096
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