| Title: |
Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index |
| Authors: |
Hoggart, CJ; Venturini, G; Mangino, M; Gomez, F; Ascari, Giulia; Zhao, JH; Teumer, A; Winkler, TW; Tsernikova, N; Luan, J; Mihailov, E; Ehret, GB; Zhang, WH; Lamparter, D; Esko, T; Mace, A; Rueger, 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; Georg, H; 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, MR; Scherag, A; Smith, GD; Borecki, IB; Rousson, V; Hirschhorn, JN; Rivolta, C; Loos, RJF; Kutalik, Z'N |
| Source: |
PLOS GENETICS ; ISSN: 1553-7390 |
| Publication Year: |
2014 |
| Collection: |
Ghent University Academic Bibliography |
| Subject Terms: |
Biology and Life Sciences; CHILDREN; ASSOCIATIONS; OBESITY; LINKAGE ANALYSIS; QUANTITATIVE TRAIT LOCI; VARIANCES; FAMILIES; GENES; ALCOHOLISM; PENETRANCE |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://biblio.ugent.be/publication/7004192; https://doi.org/10.1371/journal.pgen.1004508; https://biblio.ugent.be/publication/7004192/file/7004299 |
| DOI: |
10.1371/journal.pgen.1004508 |
| Availability: |
https://biblio.ugent.be/publication/7004192; https://hdl.handle.net/1854/LU-7004192; https://doi.org/10.1371/journal.pgen.1004508; https://biblio.ugent.be/publication/7004192/file/7004299 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.24AD49AB |
| Database: |
BASE |