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.

OriginalspracheEnglisch
Aufsatznummere1004508
ZeitschriftPLoS Genetics
Jahrgang10
Ausgabenummer7
Seiten (von - bis)1-12
Seitenumfang12
ISSN1553-7390
DOIs
PublikationsstatusVeröffentlicht - 01.01.2014

Strategische Forschungsbereiche und Zentren

  • Querschnittsbereich: Medizinische Genetik

Fingerprint

Untersuchen Sie die Forschungsthemen von „Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index“. Zusammen bilden sie einen einzigartigen Fingerprint.

Zitieren