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

Hoggart, C.J.; Venturini, G.; Mangino, M.; Gomez, F.; Ascari, G.; Zhao, J.H.; Teumer, A.; Winkler, T.W.; Ternikova, N.; Luan, J.; Mihailov, E.; Ehret, G.B.; Zhang, W.; Lamparter, D.; Esko, T.; Macé, 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.; Moradpour, D.; 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.; Santamaria, 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.; Rivolta, C.; Loos, R.J.; Kutalik, Z.

doi:10.1371/journal.pgen.1004508

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

Details

Download: BIB_B24DBE741EAD.P001.pdf (520.35 [Ko])
State: Public
Version: author

Serval ID

serval:BIB_B24DBE741EAD

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

PLoS Genetics

Author(s)

Hoggart C.J., Venturini G., Mangino M., Gomez F., Ascari G., Zhao J.H., Teumer A., Winkler T.W., Ternikova N., Luan J., Mihailov E., Ehret G.B., Zhang W., Lamparter D., Esko T., Macé 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., Moradpour D., 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., Santamaria 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., Rivolta C., Loos R.J., Kutalik Z.

Working group(s)

Generation Scotland Consortium, LifeLines Cohort study, GIANT Consortium

ISSN

1553-7404 (Electronic)

ISSN-L

1553-7390

Publication state

Published

Issued date

2014

Volume

Number

Pages

e1004508

Language

english

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.

URN

urn:nbn:ch:serval-BIB_B24DBE741EAD2

OAI-PMH

oai:serval.unil.ch:BIB_B24DBE741EAD

DOI

10.1371/journal.pgen.1004508

Pubmed

25078964

Web of science

000339902600049

Open Access

Yes