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

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. © 2014,hoggart et al.