Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index

Clive J. Hoggart; Giulia Venturini; Massimo Mangino; Felicia Gomez; Giulia Ascari; Jing Hua Zhao; Alexander Teumer; Thomas W. Winkler; Natalia Tsernikova; Jian'an Luan; Evelin Mihailov; Georg B. Ehret; Weihua Zhang; David Lamparter; Tonu Esko; Aurelien Mace; Sina Rueeger; 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; 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 Voelzke; 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; Andre Scherag; George Davey Smith; Ingrid B. Borecki; Valentin Rousson; Joel N. Hirschhorn; Carlo Rivolta; Ruth J. F. Loos; Zoltan Kutalik; LifeLines Cohort Study; Inga Prokopenko

doi:10.1371/journal.pgen.1004508

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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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Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index

Clive J. Hoggart, Giulia Venturini, Massimo Mangino, Felicia Gomez, Giulia Ascari, Jing Hua Zhao, Alexander Teumer, Thomas W. Winkler, Natalia Tsernikova, Jian'an Luan, …

PLoS genetics, Vol.10(7), pp.1-12

01/07/2014

DOI: https://doi.org/10.1371/journal.pgen.1004508

PMID: 25078964

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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 similar to 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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Title: Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index
Creators: Clive J. Hoggart - Imperial College London
Giulia Venturini - University of Lausanne
Massimo Mangino - King's College London
Felicia Gomez - Washington University in St. Louis
Giulia Ascari - University of Lausanne
Jing Hua Zhao - MRC Epidemiology Unit
Alexander Teumer - Universitätsmedizin Greifswald
Thomas W. Winkler - University of Regensburg
Natalia Tsernikova - University of Tartu
Jian'an Luan - University of Cambridge
Evelin Mihailov - University of Tartu
Georg B. Ehret - Johns Hopkins University
Weihua Zhang - Imperial College London
David Lamparter - University of Lausanne
Tonu Esko - Boston Children's Hospital
Aurelien Mace - University of Lausanne
Sina Rueeger - University of Lausanne
Pierre-Yves Bochud - Charmo University
Matteo Barcella - University of Milan
Yves Dauvilliers - Inserm
Beben Benyamin - University of Queensland
David M. Evans - University of Bristol
Caroline Hayward - MRC Institute of Genetics and Molecular Medicine
Mary F. Lopez - Harvard University
Lude Franke - University Medical Center Groningen
Alessia Russo - Italian institute for Genomic Medicine
Iris M. Heid - University of Regensburg
Erika Salvi - University of Milan
Sailaja Vendantam - Boston Children's Hospital
Dan E. Arking - Johns Hopkins University
Eric Boerwinkle - Ctr Human Genet, Houston, TX USA
John C. Chambers - Imperial College London
Giovanni Fiorito - Italian institute for Genomic Medicine
Harald Grallert - Helmholtz Zentrum München
Simonetta Guarrera - Italian institute for Genomic Medicine
Georg Homuth - Universitätsmedizin Greifswald
Jennifer E. Huffman - University of Edinburgh
David Porteous - University of Edinburgh
Darius Moradpour - College Station Medical Center
Alex Iranzo - Hospital Clínic de Barcelona
Johannes Hebebrand - University of Duisburg-Essen
John P. Kemp - University of Bristol
Gert J. Lammers - Stichting Epilepsie Instellingen Nederland
Vincent Aubert - University Hospital of Lausanne
Markus H. Heim - University Hospital of Basel
Nicholas G. Martin - QIMR Berghofer Medical Research Institute
Grant W. Montgomery - QIMR Berghofer Medical Research Institute
Rosa Peraita-Adrados - Gregorio Maranon Univ Hosp, Sleep & Epilepsy Unit, Dept Clin Neurophysiol, Madrid, Spain
Joan Santamaria - Hospital Clínic de Barcelona
Francesco Negro - Serv Clin Pathol, Serv Gastroenterol & Hepatol, Geneva, Switzerland
Carsten O. Schmidt - Universitätsmedizin Greifswald
Robert A. Scott - University of Cambridge
Tim D. Spector - King's College London
Konstantin Strauch - Helmholtz Zentrum München
Henry Voelzke - College Station Medical Center
Nicholas J. Wareham - MRC Epidemiology Unit
Wei Yuan - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Jordana T. Bell - King's College London
Aravinda Chakravarti - Johns Hopkins University
Jaspal S. Kooner - Imperial College London
Annette Peters - Helmholtz Zentrum München
Giuseppe Matullo - University of Turin
Henri Wallaschofski - Universitätsmedizin Greifswald
John B. Whitfield - QIMR Berghofer Medical Research Institute
Fred Paccaud - University Hospital of Lausanne
Peter Vollenweider - University Hospital of Lausanne
Sven Bergmann - University of Lausanne
Jacques S. Beckmann - SIB Swiss Institute of Bioinformatics
Mehdi Tafti - University Hospital of Lausanne
Nicholas D. Hastie - MRC Institute of Genetics and Molecular Medicine
Daniele Cusi - University of Milan
Murielle Bochud - University Hospital of Lausanne
Timothy M. Frayling - University of Exeter
Andres Metspalu - University of Tartu
Marjo-Riitta Jarvelin - University of Oulu
Andre Scherag - University of Duisburg-Essen
George Davey Smith - University of Bristol
Ingrid B. Borecki - Washington University in St. Louis
Valentin Rousson - University Hospital of Lausanne
Joel N. Hirschhorn - Broad Institute
Carlo Rivolta - University of Lausanne
Ruth J. F. Loos - Child Health and Development Institute
Zoltan Kutalik - SIB Swiss Institute of Bioinformatics
LifeLines Cohort Study
Inga Prokopenko - School of Biosciences
Publication Details: PLoS genetics, Vol.10(7), pp.1-12
Publisher: Public Library Science
Number of pages: 12
Date published: 01/07/2014
Grant note: 5R01MH63706:02 / NIH/NIMH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) Federal State of Mecklenburg-West Pomerania SP/04/002 / British Heart Foundation Department of Health R01DK8925601 / NIDDK; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) Ministry for Health, Welfare and Sports WT083431MA; 084723/Z/08/Z / Wellcome Trust 33CSCO-122661 / Swiss National Science Foundation GlaxoSmithKline; Swiss National Science Foundation (SNSF) British Heart Foundation German Federal Ministry of Education and Research (BMBF); Federal Ministry of Education & Research (BMBF)
Identifiers: 99928928802346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index

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