TY - JOUR AU - Hoggart, CJ AU - Venturini, G AU - Mangino, M AU - Gomez, F AU - Ascari, G AU - Zhao, JH AU - Teumer, A AU - Winkler, TW AU - Tšernikova, N AU - Luan, J AU - Mihailov, E AU - Ehret, GB AU - Zhang, W AU - Lamparter, D AU - Esko, T AU - Macé, A AU - Rüeger, S AU - Bochud, P-Y AU - Barcella, M AU - Dauvilliers, Y AU - Benyamin, B AU - Evans, DM AU - Hayward, C AU - Lopez, MF AU - Franke, L AU - Russo, A AU - Heid, IM AU - Salvi, E AU - Vendantam, S AU - Arking, DE AU - Boerwinkle, E AU - Chambers, JC AU - Fiorito, G AU - Grallert, H AU - Guarrera, S AU - Homuth, G AU - Huffman, JE AU - Porteous, D AU - Generation Scotland Consortium AU - LifeLines Cohort study AU - GIANT Consortium AU - Moradpour, D AU - Iranzo, A AU - Hebebrand, J AU - Kemp, JP AU - Lammers, GJ AU - Aubert, V AU - Heim, MH AU - Martin, NG AU - Montgomery, GW AU - Peraita-Adrados, R AU - Santamaria, J AU - Negro, F AU - Schmidt, CO AU - Scott, RA AU - Spector, TD AU - Strauch, K AU - Völzke, H AU - Wareham, NJ AU - Yuan, W AU - Bell, JT AU - Chakravarti, A AU - Kooner, JS AU - Peters, A AU - Matullo, G AU - Wallaschofski, H AU - Whitfield, JB AU - Paccaud, F AU - Vollenweider, P AU - Bergmann, S AU - Beckmann, JS AU - Tafti, M AU - Hastie, ND AU - Cusi, D AU - Bochud, M AU - Frayling, TM AU - Metspalu, A AU - Jarvelin, M-R AU - Scherag, A AU - Smith, GD AU - Borecki, IB AU - Rousson, V AU - Hirschhorn, JN AU - Rivolta, C AU - Loos, RJF AU - Kutalik, Z Y2 - 2020/12/17 Y1 - 2014/07 SN - 1553-7390 UR - http://hdl.handle.net/11343/254824 AB - 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. LA - eng PB - Public Library of Science (PLoS) T1 - Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index. DO - 10.1371/journal.pgen.1004508 IS - PLoS Genetics VL - 10 IS - 7 SP - e1004508- L1 - /bitstream/handle/11343/254824/PMC4117451.pdf?sequence=1&isAllowed=y ER -