Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.

TitreNovel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.
Publication TypeJournal Article
Year of Publication2014
AuthorsHoggart, CJ, Venturini, G, Mangino, M, Gomez, F, Ascari, G, Zhao, JHua, Teumer, A, Winkler, TW, Tšernikova, N, Luan, J'an, Mihailov, E, Ehret, GB, Zhang, W, Lamparter, D, Esko, T, Macé, A, Rüeger, S, Bochud, P-Y, 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, 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, Volzke, 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, M-R, Scherag, A, Smith, GDavey, Borecki, IB, Rousson, V, Hirschhorn, JN, Rivolta, C, Loos, RJF, Kutalik, Z
Corporate AuthorsGeneration Scotland Consortium, LifeLines Cohort Study, GIANT Consortium
JournalPLoS Genetics
Volume10
Issue7
Paginatione1004508
Date Published07/2014
DOI10.1371/journal.pgen.1004508
ISSN1553-7390 (linking)
ISBN Number1553-7404 (Electronic)
Mots-clésAdult, Body Mass Index, European Continental Ancestry Group, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomic Imprinting, Genotype, Glucose Transport Proteins, Facilitative, Humans, Male, Obesity, Polymorphism, Single Nucleotide, Potassium Channels, Tandem Pore Domain
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.

Alternate URL

http://www.ncbi.nlm.nih.gov/pubmed/25078964?dopt=Abstract

First publication date (online)

07/2014

WOS ID (UT)

000339902600049

Alternate JournalPLoS Genet.
Citation Key / SERVAL ID3593
Peer reviewRefereed
PubMed ID25078964
PubMed Central IDPMC4117451
Grant List084723/Z/08/Z / / Wellcome Trust / United Kingdom
0927310 / / Medical Research Council / United Kingdom
0927310 / / Wellcome Trust / United Kingdom
097117 / / Wellcome Trust / United Kingdom
1RL1MH083268-01 / MH / NIMH NIH HHS / United States
5R01HL087679-02 / HL / NHLBI NIH HHS / United States
5R01MH63706:02 / MH / NIMH NIH HHS / United States
AA014041 / AA / NIAAA NIH HHS / United States
AA07535 / AA / NIAAA NIH HHS / United States
AA10248 / AA / NIAAA NIH HHS / United States
AA13320 / AA / NIAAA NIH HHS / United States
AA13321 / AA / NIAAA NIH HHS / United States
AA13326 / AA / NIAAA NIH HHS / United States
BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
CZD/16/6/4 / / Chief Scientist Office / United Kingdom
DA12854 / DA / NIDA NIH HHS / United States
G0100266 / / Medical Research Council / United Kingdom
G0500539 / / Medical Research Council / United Kingdom
G0600705 / / Medical Research Council / United Kingdom
G0601966 / / Medical Research Council / United Kingdom
G0700931 / / Medical Research Council / United Kingdom
G0701863 / / Medical Research Council / United Kingdom
G1002319 / / Medical Research Council / United Kingdom
G9815508 / / Medical Research Council / United Kingdom
HHSN268200625226C / / PHS HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100006C / / PHS HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100010C / / PHS HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
MC_PC_15018 / / Medical Research Council / United Kingdom
MC_PC_U127561128 / / Medical Research Council / United Kingdom
MC_U106179471 / / Medical Research Council / United Kingdom
MC_UP_0801/1 / / Medical Research Council / United Kingdom
MC_UU_12013/1 / / Medical Research Council / United Kingdom
MC_UU_12015/1 / / Medical Research Council / United Kingdom
MR/K013351/1 / / Medical Research Council / United Kingdom
MR/K026992/1 / / Medical Research Council / United Kingdom
P30 DK079637 / DK / NIDDK NIH HHS / United States
R01DK8925601 / DK / NIDDK NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
T32 HL091823 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
WT083431MA / / Wellcome Trust / United Kingdom

                         

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