@article{d09d264aedc742d8a66cf05a97edd24a,
title = "Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index",
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 similar to 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",
author = "Hoggart, {Clive J.} and Giulia Venturini and Massimo Mangino and Felicia Gomez and Giulia Ascari and Zhao, {Jing Hua} and Alexander Teumer and Winkler, {Thomas W.} and Natalia T{\v s}ernikova and Jian'an Luan and Evelin Mihailov and Ehret, {Georg B.} and Weihua Zhang and David Lamparter and T{\~o}nu Esko and Aurelien Mac{\'e} and Sina R{\"u}eger and Pierre-Yves Bochud and Matteo Barcella and Yves Dauvilliers and Beben Benyamin and Evans, {David M.} and Caroline Hayward and Lopez, {Mary F.} and Lude Franke and Alessia Russo and Heid, {Iris M.} and Erika Salvi and Sailaja Vendantam and Arking, {Dan E.} and Eric Boerwinkle and Chambers, {John C.} and Giovanni Fiorito and Harald Grallert and Simonetta Guarrera and Georg Homuth and Huffman, {Jennifer E.} and David Porteous and Darius Moradpour and Alex Iranzo and Johannes Hebebrand and Kemp, {John P.} and Lammers, {Gert J.} and Vincent Aubert and Heim, {Markus H.} and Martin, {Nicholas G.} and Montgomery, {Grant W.} and Rosa Peraita-Adrados and {AUTHOR GROUP} and Trip, {Mieke D.} and Hovingh, {Kees G.} and J.J. Hottenga and G. Willemsen and D.I. Boomsma and B.W.J.H. Penninx and A.G. Uitterlinden and {van Duijn}, C.M. and P.M. Visscher and V. Rousson and J.N. Hirschhorn and C. Rivolta and R.J.F. Loos and Z. Kutali",
year = "2014",
doi = "https://doi.org/10.1371/journal.pgen.1004508",
language = "English",
volume = "10",
pages = "e1004508",
journal = "PLoS genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "7",
}