Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index
In: PLOS GENETICS, 2014, Heft 7, S. e1004508-e1004508
Online
academicJournal
Zugriff:
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.
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Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index
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| Autor/in / Beteiligte Person: | Visscher, Peter M. ; Hoggart, Clive J. ; Venturini, Giulia ; Mangino, Massimo ; Gomez, Felicia ; Ascari, Giulia ; Jing Hua Zhao ; 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 ; Pierre Yves Bochud ; 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. ; Rosa Peraita Adrados ; 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 ; Marjo Riitta Jarvelin ; Scherag, André ; George Davey Smith ; Borecki, Ingrid B. ; Rousson, Valentin ; Hirschhorn, Joel N. ; Rivolta, Carlo ; Loos, Ruth J. F. ; Kutalik, Zoltán ; Bochud, Pierre-Yves ; Dauvillier, Yves ; Evan, David M. ; Russo, Alessia ; Chamber, John C. ; Fiorito, Giovanni ; Guarrera, Simonetta ; Porteou, David ; Lammer, Gert J. ; Peraita-Adrado, Rosa ; Negro, Francesco ; Peter, Annette ; Matullo, Giuseppe ; Jarvelin, Marjo-Riitta ; Loo, Ruth J. F. |
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| Zeitschrift: | PLOS GENETICS, 2014, Heft 7, S. e1004508-e1004508 |
| Veröffentlichung: | 2014 |
| Medientyp: | academicJournal |
| DOI: | 10.1371/journal.pgen.1004508 |
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