biostudies-literatureHoggart CJEconomic and Social Research CouncilBritish Heart FoundationNCRR NIH HHSNIDA NIH HHSNHLBI NIH HHSNIMH NIH HHSNIAAA NIH HHSRNIDSwiss National Science FoundationNIDDK NIH HHSMedical Research CouncilDutch Research Council (NWO)Chief Scientist OfficeNHGRI NIH HHSNational Institute for Health Research (NIHR)Wellcome TrustNovo Nordisk FondenPHS HHSBiotechnology and Biological Sciences Research Councile1004508https://www.ebi.ac.uk/biostudies/studies/S-EPMC4117451biostudies-literatureUnknown10(7)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 materPLoS geneticsNovel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index.PMC4117451AA13320G050053910371NNF13OC0005785R01 DA0128540927310R01 HL087679R01 HL059367HHSN268201100009IHHSN268201100005CT32 HL091823NF-SI-0513-10151P30 DK079637NNF14OC0010513UL1 RR025005HHSN268201100009CRG/09/012/28096AA13321G0100266HHSN268201100005IMC_PC_15018T32 HL007055R01HL087641AA13326HHSN268201100005GR01 AA007535R01 MH063706G51BB/F019394/1NF-SI-0510-10214MR/K026992/1097117R01DK8925601G0701863R01HL59367HHSN268201100006CMR/K006584/1MC_PC_U127561128G0700931HHSN268201100010CR01 HL086694AA102481439141RL1MH083268-01MC_UP_0801/1WT083431MAU01 HG004402175.010.200HHSN268201100011IR01 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AJHunt SEBalmforth AJBeckmann JSTeumer APell JShi Jvan Rossum LLakka TAHicks AAMedina-Gomez CFord IStefansson KBoerwinkle EMonda KLAbecasis GROhlsson CJarick ISanders ARBochud PYUre JHveem KVedantam SStumvoll MSpector TDBultmann UWood ARGustafsson SBragg-Gresham JLStrawbridge RJDeary IOostra BAWang ZCookson WFrau FYang JWright AFRadhakrishnan AAlizadeh BWallaschofski HFarrall MMooser VHamsten AKee FWolffenbuttel BHPolasek OIranzo ASkrobek BSteinthorsdottir VVendantam SPower CSchlessinger DSoranzo NLehtimaki TChakravarti AKarpe FStrachan DPLangenberg CZillikens MFiorito GMagnusson PKCampbell HSmith GDVan der Klauw MMPalmer CStirrups KHovingh KGShin SYWorkalemahu TLindstrom JfalseNovel 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 mater2014-01-01T00:00:00Z2014 Jul2026-05-04T23:22:14.549Z2019-03-27T01:33:08ZS-EPMC41174512507896410.1371/journal.pgen.1004508