Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index
Journal article
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, ... Lorentzon, Mattias*. (2014). Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index. PLoS Genetics. 10(7), p. e1004508. https://doi.org/10.1371/journal.pgen.1004508
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, Generation Scotland Consortium, The LifeLines Cohort Study, The 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 J. F., Kutalik, Zoltán and Lorentzon, Mattias* |
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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. |
Year | 2014 |
Journal | PLoS Genetics |
Journal citation | 10 (7), p. e1004508 |
Publisher | Public Library of Science |
ISSN | 1553-7390 |
Digital Object Identifier (DOI) | https://doi.org/10.1371/journal.pgen.1004508 |
Scopus EID | 2-s2.0-84905474692 |
Open access | Published as ‘gold’ (paid) open access |
Research or scholarly | Research |
Page range | 1-12 |
Funder | Australian Research Council (ARC) |
National Health and Medical Research Council (NHMRC) | |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 31 Jul 2014 |
Publication process dates | |
Accepted | 14 May 2014 |
Deposited | 11 Aug 2021 |
ARC Funded Research | This output has been funded, wholly or partially, under the Australian Research Council Act 2001 |
Grant ID | NHMRC/241944 |
NHMRC/389875 | |
NHMRC/389891 | |
NHMRC/389892 | |
NHMRC/389938 | |
NHMRC/442915 | |
NHMRC/442981 | |
NHMRC/496739 | |
NHMRC/496688 | |
NHMRC/552485 | |
NHMRC/613672 | |
ARC/DP0770096 | |
Additional information | *Member of the Genetic Investigation of ANthropometric |
https://acuresearchbank.acu.edu.au/item/8w941/novel-approach-identifies-snps-in-slc2a10-and-kcnk9-with-evidence-for-parent-of-origin-effect-on-body-mass-index
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Publisher's version
OA_Hoggart_2014_Novel_approach_identifies_SNPs_in_SLC2A10.pdf | |
License: CC BY 4.0 | |
File access level: Open |
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