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Get Free AccessThe 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.
Clive Hoggart, Giulia Venturini, Massimo Mangino, Felicia Gomez, Giulia Ascari, Jing Hua Zhao, Alexander Teumer, Thomas W. Winkler, Natalia Tšernikova, Jian'an Luan, Evelin Mihailov, Georg Ehret, Weihua Zhang, David Lamparter, Tõnu Esko, Aurélien Macé, Sina Rüeger, Pierre–Yves Bochud, Matteo Barcella, Yves Dauvilliers, Beben Benyamin, David M. Evans, Caroline Hayward, Mary F. Lopez, Lude Franke, Alessia Russo, Iris M. Heid, Erika Salvi, Sailaja Vendantam, Dan E. Arking, Eric Boerwinkle, John C. Chambers, Giovanni Fiorito, Harald Grallert, Simonetta Guarrera, Georg Homuth, Jennifer E. Huffman, David J. Porteous, Darius Moradpour, Álex Iranzo, Johannes Hebebrand, John P. Kemp, Gert Jan Lammers, Vincent Aubert, Markus H. Heim, Nicholas G. Martin, Grant W. Montgomery, Rosa Peraita‐Adrados, Joan Santamaría, Francesco Negro, Carsten Oliver Schmidt, Robert A. Scott, Tim D. Spector, Konstantin Strauch, Henry Völzke, Nicholas J. Wareham, Yuan Wei, Jordana T. Bell, Aravinda Chakravarti, Jaspal S. Kooner, Annette Peters, Giuseppe Matullo, Henri Wallaschofski, John B. Whitfield, Fred Paccaud, Péter Vollenweider, Sven Bergmann, J. Beckmann, Mehdi Tafti, Nicholas D. Hastie, Daniele Cusi, Murielle Bochud, Timothy M Frayling, Andres Metspalu, Paul M Ridker, André Scherag, George Davey Smith, Ingrid B. Borecki, Valentin Rousson, Joel N. Hirschhorn, Carlo Rivolta, Ruth J. F. Loos, Zoltán Kutalik (2014). Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index. , 10(7), DOI: https://doi.org/10.1371/journal.pgen.1004508.
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Type
Article
Year
2014
Authors
83
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1371/journal.pgen.1004508
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