|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Hoggart, CJ, Venturini, G, Mangino, M, Gomez, F, Ascari, G, Zhao, JH, Teumer, A, Winkler, TW, Tšernikova, N, Luan, J, Mihailov, E, Ehret, GB, Zhang, W, Lamparter, D, Esko, T, Macé, A, Rüeger, S, Bochud, PY, Barcella, M, Dauvilliers, Y, Benyamin, B, Evans, DM, Hayward, C, Lopez, MF, Franke, L, Russo, A, Heid, IM, Salvi, E, Vendantam, S, Arking, DE, Boerwinkle, E, Chambers, JC, Fiorito, G, Grallert, H, Guarrera, S, Homuth, G, Huffman, JE, Porteous, D, Generation Scotland, C, study LifeLines Cohort, , GIANT, C, Moradpour, D, Iranzo, A, Hebebrand, J, Kemp, JP, Lammers, GJ, Aubert, V, Heim, MH, Martin, NG, Montgomery, GW, Peraita-Adrados, R, Santamaria, J, Negro, F, Schmidt, CO, Scott, RA, Spector, TD, Strauch, K, Völzke, H, Wareham, NJ, Yuan, W, Bell, JT, Chakravarti, A, Kooner, JS, Peters, A, Matullo, G, Wallaschofski, H, Whitfield, JB, Paccaud, F, Vollenweider, P, Bergmann, S, Beckmann, JS, Tafti, M, Hastie, ND, Cusi, D, Bochud, M, Frayling, TM, Metspalu, A, Jarvelin, MR, Scherag, A, Smith, GD, Borecki, IB, Rousson, V, Hirschhorn, JN, Rivolta, C, Loos, RJ, Kutalik, Z|
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.