In: PLOS Genetics
10(7), e1004508
[PDF, 549kB]
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.
Item Type: | Journal article |
---|---|
Faculties: | Medicine > Institute for Medical Information Processing, Biometry and Epidemiology |
Subjects: | 600 Technology > 610 Medicine and health |
URN: | urn:nbn:de:bvb:19-epub-33545-6 |
ISSN: | 1553-7390 |
Language: | English |
Item ID: | 33545 |
Date Deposited: | 15. Feb 2017, 14:45 |
Last Modified: | 09. Jun 2022, 15:08 |