Please use this identifier to cite or link to this item:
https://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 |
Editor: | Visscher, P. |
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 Female Male Glucose Transport Proteins, Facilitative Genome-Wide Association Study White People |
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. |
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 |
Published version: | http://dx.doi.org/10.1371/journal.pgen.1004508 |
Appears in Collections: | Aurora harvest 7 Public Health publications |
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