Please use this identifier to cite or link to this item:
Title: Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index
Authors: Hoggart, Clive J.;Venturini, Giulia;Mangino, Massimo;Gomez, Felicia;Ascari, Giulia;Zhao, Jing Hua;Teumer, Alexander;Winkler, Thomas W.;Tšernikova, Natalia;Luan, Jian'an;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;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 J. F.;Kutalik, Zoltán
subject: Physical Sciences;Mathematics;Statistics (Mathematics);Biostatistics;Statistical Methods;Biology and Life Sciences;Computational Biology;Genome Analysis;Genome-Wide Association Studies;Epigenomics;Developmental Biology;Genomic Imprinting;Genetics;Epigenetics;Genomics
Year: 2014
Publisher: Public Library of Science
Description: 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.
Standard no: Hoggart, C. J., G. Venturini, M. Mangino, F. Gomez, G. Ascari, J. H. Zhao, A. Teumer, et al. 2014. “Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index.” PLoS Genetics 10 (7): e1004508. doi:10.1371/journal.pgen.1004508.
Appears in Collections:HMS Scholarly Articles

Files in This Item:
Click on the URI links for accessing contents.

Items in HannanDL are protected by copyright, with all rights reserved, unless otherwise indicated.