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Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index

Hoggart, Clive J. and Venturini, Giulia and Mangino, Massimo and Gomez, Felicia and Ascari, Giulia and Zhao, Jing Hua and Teumer, Alexander and Winkler, Thomas W. and Tšernikova, Natalia and Luan, Jian'an and Mihailov, Evelin and Ehret, Georg B. and Zhang, Weihua and Lamparter, David and Esko, Tõnu and Macé, Aurelien and Rüeger, Sina and Bochud, Pierre-Yves and Barcella, Matteo and Dauvilliers, Yves and Benyamin, Beben and Evans, David M. and Hayward, Caroline and Lopez, Mary F. and Franke, Lude and Russo, Alessia and Heid, Iris M. and Salvi, Erika and Vendantam, Sailaja and Arking, Dan E. and Boerwinkle, Eric and Chambers, John C. and Fiorito, Giovanni and Grallert, Harald and Guarrera, Simonetta and Homuth, Georg and Huffman, Jennifer E. and Porteous, David and Generation Scotland Consortium, and LifeLines Cohort study, and Giant Consortium, and Moradpour, Darius and Iranzo, Alex and Hebebrand, Johannes and Kemp, John P. and Lammers, Gert J. and Aubert, Vincent and Heim, Markus H. and Martin, Nicholas G. and Montgomery, Grant W. and Peraita-Adrados, Rosa and Santamaria, Joan and Negro, Francesco and Schmidt, Carsten O. and Scott, Robert A. and Spector, Tim D. and Strauch, Konstantin and Völzke, Henry and Wareham, Nicholas J. and Yuan, Wei and Bell, Jordana T. and Chakravarti, Aravinda and Kooner, Jaspal S. and Peters, Annette and Matullo, Giuseppe and Wallaschofski, Henri and Whitfield, John B. and Paccaud, Fred and Vollenweider, Peter and Bergmann, Sven and Beckmann, Jacques S. and Tafti, Mehdi and Hastie, Nicholas D. and Cusi, Daniele and Bochud, Murielle and Frayling, Timothy M. and Metspalu, Andres and Jarvelin, Marjo-Riitta and Scherag, André and Smith, George Davey and Borecki, Ingrid B. and Rousson, Valentin and Hirschhorn, Joel N. and Rivolta, Carlo and Loos, Ruth J. F. and Kutalik, Zoltán. (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.

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Official URL: https://edoc.unibas.ch/61763/

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Hepatologie > Hepatologie (Heim)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Hepatologie > Hepatologie (Heim)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Hepatology Laboratory (Heim)
UniBasel Contributors:Heim, Markus H.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
ISSN:1553-7390
e-ISSN:1553-7404
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:23 Jul 2020 11:47
Deposited On:23 Jul 2020 11:47

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