PLoS Genetics (Jul 2014)

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 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

DOI
https://doi.org/10.1371/journal.pgen.1004508
Journal volume & issue
Vol. 10, no. 7
p. e1004508

Abstract

Read online

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.