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

作者：Hoggart Clive J^*; Venturini Giulia; Mangino Massimo; Gomez Felicia; Ascari Giulia; Zhao Jing Hua; Teumer Alexander; Winkler Thomas W; Tsernikova Natalia; Luan Jian' an; Mihailov Evelin; Ehret Georg B; Zhang Weihua; Lamparter David; Esko Tonu; Mace Aurelien; Rueeger Sina; Bochud Pierre Yves; Barcella Matteo; Dauvilliers Yves; Benyamin Beben; Evans David M; Hayward Caroline; Lopez Mary F; Franke Lude; Russo Alessia; Heid Iris M; Salvi Erika

来源：PLoS Genetics, 2014, 10(7): e1004508.

DOI：10.1371/journal.pgen.1004508

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 %26gt;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 %26lt; 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 %26lt; 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.

• 出版日期2014-7
• 单位河北医科大学