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Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index.
- Source :
-
PLoS Genetics . Jul2014, Vol. 10 Issue 7, p1-12. 12p. - Publication Year :
- 2014
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15537390
- Volume :
- 10
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- PLoS Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 97291287
- Full Text :
- https://doi.org/10.1371/journal.pgen.1004508