Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.
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Authors
Hoggart, Clive J
Venturini, Giulia
Mangino, Massimo
Gomez, Felicia
Ascari, Giulia
Zhao, Jing Hua
Teumer, Alexander
Winkler, Thomas W
Tšernikova, Natalia
Mihailov, Evelin
Ehret, Georg B
Zhang, Weihua
Lamparter, David
Esko, Tõnu
Macé, Aurelien
Rüeger, Sina
Bochud, Pierre-Yves
Barcella, Matteo
Dauvilliers, Yves
Benyamin, Beben
Evans, David M
Hayward, Caroline
Lopez, Mary F
Franke, Lude
Russo, Alessia
Heid, Iris M
Salvi, Erika
Vendantam, Sailaja
Arking, Dan E
Boerwinkle, Eric
Chambers, John C
Fiorito, Giovanni
Grallert, Harald
Guarrera, Simonetta
Homuth, Georg
Huffman, Jennifer E
Porteous, David
Generation Scotland Consortium
LifeLines Cohort study
GIANT Consortium
Moradpour, Darius
Iranzo, Alex
Hebebrand, Johannes
Kemp, John P
Lammers, Gert J
Aubert, Vincent
Heim, Markus H
Martin, Nicholas G
Montgomery, Grant W
Peraita-Adrados, Rosa
Santamaria, Joan
Negro, Francesco
Schmidt, Carsten O
Scott, Robert A
Spector, Tim D
Strauch, Konstantin
Völzke, Henry
Wareham, Nicholas J
Yuan, Wei
Bell, Jordana T
Chakravarti, Aravinda
Kooner, Jaspal S
Peters, Annette
Matullo, Giuseppe
Wallaschofski, Henri
Whitfield, John B
Paccaud, Fred
Vollenweider, Peter
Bergmann, Sven
Beckmann, Jacques S
Tafti, Mehdi
Hastie, Nicholas D
Cusi, Daniele
Bochud, Murielle
Frayling, Timothy M
Metspalu, Andres
Jarvelin, Marjo-Riitta
Scherag, André
Smith, George Davey
Borecki, Ingrid B
Rousson, Valentin
Hirschhorn, Joel N
Rivolta, Carlo
Loos, Ruth JF
Kutalik, Zoltán
Publication Date
2014-07Journal Title
PLoS Genet
ISSN
1553-7390
Publisher
Public Library of Science (PLoS)
Volume
10
Issue
7
Pages
e1004508
Language
eng
Type
Article
Physical Medium
Electronic-eCollection
Metadata
Show full item recordCitation
Hoggart, C. J., Venturini, G., Mangino, M., Gomez, F., Ascari, G., Zhao, J. H., Teumer, A., et al. (2014). Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.. PLoS Genet, 10 (7), e1004508. https://doi.org/10.1371/journal.pgen.1004508
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
Sponsorship
Medical Research Council (MC_UU_12015/1)
Medical Research Council (G0701863)
Medical Research Council (MC_U106179471)
British Heart Foundation (None)
European Commission (279143)
Identifiers
External DOI: https://doi.org/10.1371/journal.pgen.1004508
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284876
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