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Title

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

Authors
Hoggart, Clive J
Venturini, Giulia
Mangino, Massimo
Gomez, Felicia
Ascari, Giulia
Zhao, Jing Hua
Teumer, Alexander
Winkler, Thomas W
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Collaboration
Published in PLOS Genetics. 2014, vol. 10, no. 7, p. e1004508
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.
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PMID: 25078964
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Article (Author postprint) (537 Kb) - public document Free access
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Research group Etudes et traitement de l'hépatite C et B (554)
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(ISO format)
HOGGART, Clive J et al. Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index. In: PLOS Genetics, 2014, vol. 10, n° 7, p. e1004508. https://archive-ouverte.unige.ch/unige:39263

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Deposited on : 2014-08-07

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