Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.
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 ge...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-07-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1004508 |
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| author | Clive J 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 B Ehret Weihua Zhang David Lamparter Tõnu Esko Aurelien 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 Porteous Generation Scotland Consortium LifeLines Cohort study GIANT Consortium Darius Moradpour Alex Iranzo Johannes Hebebrand John P Kemp Gert J Lammers Vincent Aubert Markus H Heim Nicholas G Martin Grant W Montgomery Rosa Peraita-Adrados Joan Santamaria Francesco Negro Carsten O Schmidt Robert A Scott Tim D Spector Konstantin Strauch Henry Völzke Nicholas J Wareham Wei Yuan Jordana T Bell Aravinda Chakravarti Jaspal S Kooner Annette Peters Giuseppe Matullo Henri Wallaschofski John B Whitfield Fred Paccaud Peter Vollenweider Sven Bergmann Jacques S Beckmann Mehdi Tafti Nicholas D Hastie Daniele Cusi Murielle Bochud Timothy M Frayling Andres Metspalu Marjo-Riitta Jarvelin André Scherag George Davey Smith Ingrid B Borecki Valentin Rousson Joel N Hirschhorn Carlo Rivolta Ruth J F Loos Zoltán Kutalik |
| author_facet | Clive J 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 B Ehret Weihua Zhang David Lamparter Tõnu Esko Aurelien 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 Porteous Generation Scotland Consortium LifeLines Cohort study GIANT Consortium Darius Moradpour Alex Iranzo Johannes Hebebrand John P Kemp Gert J Lammers Vincent Aubert Markus H Heim Nicholas G Martin Grant W Montgomery Rosa Peraita-Adrados Joan Santamaria Francesco Negro Carsten O Schmidt Robert A Scott Tim D Spector Konstantin Strauch Henry Völzke Nicholas J Wareham Wei Yuan Jordana T Bell Aravinda Chakravarti Jaspal S Kooner Annette Peters Giuseppe Matullo Henri Wallaschofski John B Whitfield Fred Paccaud Peter Vollenweider Sven Bergmann Jacques S Beckmann Mehdi Tafti Nicholas D Hastie Daniele Cusi Murielle Bochud Timothy M Frayling Andres Metspalu Marjo-Riitta Jarvelin André Scherag George Davey Smith Ingrid B Borecki Valentin Rousson Joel N Hirschhorn Carlo Rivolta Ruth J F Loos Zoltán Kutalik |
| author_sort | Clive J Hoggart |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-6b5ebe329cc640c482a2dc731b70d7f4 |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2014-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-6b5ebe329cc640c482a2dc731b70d7f42025-08-20T03:46:43ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-07-01107e100450810.1371/journal.pgen.1004508Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.Clive J HoggartGiulia VenturiniMassimo ManginoFelicia GomezGiulia AscariJing Hua ZhaoAlexander TeumerThomas W WinklerNatalia TšernikovaJian'an LuanEvelin MihailovGeorg B EhretWeihua ZhangDavid LamparterTõnu EskoAurelien MacéSina RüegerPierre-Yves BochudMatteo BarcellaYves DauvilliersBeben BenyaminDavid M EvansCaroline HaywardMary F LopezLude FrankeAlessia RussoIris M HeidErika SalviSailaja VendantamDan E ArkingEric BoerwinkleJohn C ChambersGiovanni FioritoHarald GrallertSimonetta GuarreraGeorg HomuthJennifer E HuffmanDavid PorteousGeneration Scotland ConsortiumLifeLines Cohort studyGIANT ConsortiumDarius MoradpourAlex IranzoJohannes HebebrandJohn P KempGert J LammersVincent AubertMarkus H HeimNicholas G MartinGrant W MontgomeryRosa Peraita-AdradosJoan SantamariaFrancesco NegroCarsten O SchmidtRobert A ScottTim D SpectorKonstantin StrauchHenry VölzkeNicholas J WarehamWei YuanJordana T BellAravinda ChakravartiJaspal S KoonerAnnette PetersGiuseppe MatulloHenri WallaschofskiJohn B WhitfieldFred PaccaudPeter VollenweiderSven BergmannJacques S BeckmannMehdi TaftiNicholas D HastieDaniele CusiMurielle BochudTimothy M FraylingAndres MetspaluMarjo-Riitta JarvelinAndré ScheragGeorge Davey SmithIngrid B BoreckiValentin RoussonJoel N HirschhornCarlo RivoltaRuth J F LoosZoltán KutalikThe 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.https://doi.org/10.1371/journal.pgen.1004508 |
| spellingShingle | Clive J 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 B Ehret Weihua Zhang David Lamparter Tõnu Esko Aurelien 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 Porteous Generation Scotland Consortium LifeLines Cohort study GIANT Consortium Darius Moradpour Alex Iranzo Johannes Hebebrand John P Kemp Gert J Lammers Vincent Aubert Markus H Heim Nicholas G Martin Grant W Montgomery Rosa Peraita-Adrados Joan Santamaria Francesco Negro Carsten O Schmidt Robert A Scott Tim D Spector Konstantin Strauch Henry Völzke Nicholas J Wareham Wei Yuan Jordana T Bell Aravinda Chakravarti Jaspal S Kooner Annette Peters Giuseppe Matullo Henri Wallaschofski John B Whitfield Fred Paccaud Peter Vollenweider Sven Bergmann Jacques S Beckmann Mehdi Tafti Nicholas D Hastie Daniele Cusi Murielle Bochud Timothy M Frayling Andres Metspalu Marjo-Riitta Jarvelin André Scherag George Davey Smith Ingrid B Borecki Valentin Rousson Joel N Hirschhorn Carlo Rivolta Ruth J F Loos Zoltán Kutalik Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index. PLoS Genetics |
| title | Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index. |
| title_full | Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index. |
| title_fullStr | Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index. |
| title_full_unstemmed | Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index. |
| title_short | Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index. |
| title_sort | novel approach identifies snps in slc2a10 and kcnk9 with evidence for parent of origin effect on body mass index |
| url | https://doi.org/10.1371/journal.pgen.1004508 |
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