PuSH - Publikationsserver des Helmholtz Zentrums München: Novel approach identifies SNPs in <em>SLC2A10</em> and <em>KCNK9</em> with evidence for parent-of-origin effect on Body Mass Index.

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Hoggart, C.J.* ; Venturini, G.* ; Mangino, M.* ; Gomez, F.* ; Ascari, G.* ; Zhao, J.H.* ; Teumer, A.* ; Winkler, T.W.* ; Tsernikova, N.* ; Luan, J.* ; Mihailov, E.* ; Ehret, G.B.* ; Zhang, W.* ; Lamparter, D.* ; Esko, T.* ; Mace, A.* ; Rüeger, S.* ; Bochud, P.Y.* ; Barcella, M.* ; Dauvilliers, Y.* ; Benyamin, B.* ; Evans, D.M* ; Hayward, C.* ; Lopez, M.F.* ; Franke, L.* ; Russo, A.* ; Heid, I.M.* ; Salvi, E.* ; Vendantam, S.* ; Arking, D.E.* ; Boerwinkle, E.* ; Chambers, J.C.* ; Fiorito, G.* ; Grallert, H. ; Guarrera, S.* ; Homuth, G.* ; Huffman, J.E.* ; Porteous, D.J.* ; Generation Scotland Consortium (Loos, R.J.*) ; LifeLines Cohort Study (Rivolta, C.*) ; GIANT Consortium (Albrecht, E. ; Gieger, C. ; Heid, I.M. ; Illig, T. ; Kutalik, Z.* ; Müller-Nurasyid, M. ; Thorand, B. ; Wichmann, H.-E.) ; Moradpour, D.* ; Iranzo, A.* ; Hebebrand, J.* ; Kemp, J.P.* ; Lammers, G.J.* ; Aubert, V.* ; Heim, M.H.* ; Martin, N.G.* ; Montgomery, G.W.* ; Peraita-Adrados, R.* ; Santamaría, J.* ; Negro, F.* ; Schmidt, C.O.* ; Scott, R.A.* ; Spector, T.D.* ; Strauch, K. ; Völzke, H.* ; Wareham, N.J.* ; Yuan, W.* ; Bell, J.T.* ; Chakravarti, A.* ; Kooner, J.S.* ; Peters, A. ; Matullo, G.* ; Wallaschofski, H.* ; Whitfield, J.B.* ; Paccaud, F.* ; Vollenweider, P.* ; Bergmann, S.* ; Beckmann, J.S.* ; Tafti, M.* ; Hastie, N.D.* ; Cusi, D.* ; Bochud, M.* ; Frayling, T.M.* ; Metspalu, A.* ; Jarvelin, M.R.* ; Scherag, A.* ; Smith, G.D.* ; Borecki, I.B.* ; Rousson, V.* ; Hirschhorn, J.N.*

Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on Body Mass Index.

PLoS Genet. 10, 1-12:e1004508 (2014)

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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.

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