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

(2014) PLOS GENETICS. 10(7).
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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.
Keywords
CHILDREN, ASSOCIATIONS, OBESITY, LINKAGE ANALYSIS, QUANTITATIVE TRAIT LOCI, VARIANCES, FAMILIES, GENES, ALCOHOLISM, PENETRANCE

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Chicago
Hoggart, CJ, G Venturini, M Mangino, F Gomez, Giulia Ascari, JH Zhao, A Teumer, et al. 2014. “Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-origin Effect on Body Mass Index.” Plos Genetics 10 (7).
APA
Hoggart, C., Venturini, G., Mangino, M., Gomez, F., Ascari, G., Zhao, J., Teumer, A., et al. (2014). Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index. PLOS GENETICS, 10(7).
Vancouver
1.
Hoggart C, Venturini G, Mangino M, Gomez F, Ascari G, Zhao J, et al. Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index. PLOS GENETICS. 2014;10(7).
MLA
Hoggart, CJ et al. “Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-origin Effect on Body Mass Index.” PLOS GENETICS 10.7 (2014): n. pag. Print.
@article{7004192,
  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 {\textrangle}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 {\textlangle} 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 {\textlangle} 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.},
  articleno    = {e1004508},
  author       = {Hoggart, CJ and Venturini, G and Mangino, M and Gomez, F and Ascari, Giulia and Zhao, JH and Teumer, A and Winkler, TW and Tsernikova, N and Luan, J and Mihailov, E and Ehret, GB and Zhang, WH and Lamparter, D and Esko, T and Mace, A and Rueger, S and Bochud, PY and Barcella, M and Dauvilliers, Y and Benyamin, B and Evans, DM and Hayward, C and Lopez, MF and Franke, L and Russo, A and Heid, IM and Salvi, E and Vendantam, S and Arking, DE and Boerwinkle, E and Chambers, JC and Fiorito, G and Grallert, H and Guarrera, S and Georg, H and Huffman, JE and Porteous, D and Moradpour, D and Iranzo, A and Hebebrand, J and Kemp, JP and Lammers, GJ and Aubert, V and Heim, MH and Martin, NG and Montgomery, GW and Peraita-Adrados, R and Santamaria, J and Negro, F and Schmidt, CO and Scott, RA and Spector, TD and Strauch, K and Volzke, H and Wareham, NJ and Yuan, W and Bell, JT and Chakravarti, A and Kooner, JS and Peters, A and Matullo, G and Wallaschofski, H and Whitfield, JB and Paccaud, F and Vollenweider, P and Bergmann, S and Beckmann, JS and Tafti, M and Hastie, ND and Cusi, D and Bochud, M and Frayling, TM and Metspalu, A and Jarvelin, MR and Scherag, A and Smith, GD and Borecki, IB and Rousson, V and Hirschhorn, JN and Rivolta, C and Loos, RJF and Kutalik, Z'N},
  issn         = {1553-7390},
  journal      = {PLOS GENETICS},
  language     = {eng},
  number       = {7},
  pages        = {12},
  title        = {Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index},
  url          = {http://dx.doi.org/10.1371/journal.pgen.1004508},
  volume       = {10},
  year         = {2014},
}

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