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

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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.

authors

  • Meyre, David Jean-Claude
  • 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
  • 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 JF
  • Kutalik, Zoltán

publication date

  • July 2014