Contributions
Abstract: P431
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Genetics/Epigenetics
Introduction: Parent-of-origin effect describes a phenotype that depends on whether a causative allele was inherited from the mother or the father.
Objectives: We aimed to investigate whether any parent-of-origin effects are observed in multiple sclerosis (MS) susceptibility.
Methods: We utilized a genome-wide single nucleotide polymorphism (SNP) dataset of 931 family trios (consisting of an affected child and both parents) of European origin. After strand phasing and SNP imputation, parent-of-origin effects were analyzed with the PREMIM/EMIM software. For each SNP, p values for maternal and paternal inheritance effects were assessed and those with p < 0.05 were evaluated.
Results: Out of 198 MS risk-associated non-MHC SNPs available on the chip, 24 had nominal statistically significant maternal parent-of-origin effects, whereas 21 had nominal paternal parent-of-origin effects. None of them passed the genome-wide significance threshold. However, in the EVI5 region in chromosome 1 where multiple independent MS risk-variants were identified, a SNP closest to GFI1 previously shown to be paternally expressed, displays paternal parent-of-origin effect for MS risk (rs58394161, p = 0.0099).
Conclusions: We analyzed parent-of-origin effects in MS and identified MS-associated variants with potential parent-of-origin effects on disease susceptibility. Parent-of-origin effects in regions with multiple independent MS variants may provide important clues on the functional mechanisms that contribute to MS risk and could partially explain the missing heritability in MS.
Disclosure: Noriko Isobe: received grant support from JSPS Kakenhi 18K07529, Japan Intractable Disease research Foundation, Japan Multiple Sclerosis Society, Mitsubishi Tanabe Pharma, Bayer Yakuhin, Ltd., and Japan Blood Products Organization. Andy Tsai: nothing to disclose. Stacy J Caillier: nothing to disclose.Adam Santaniello: nothing to disclose. Jun-ichi Kira: received rants, consultant fees, speaking fees and/or honoraria from AMED, Health, Labour and Welfare Sciences Research Grants, MEXT KAKENHI, JSPS KAKENHI, Novartis Pharma, Mitsubishi Tanabe Pharma, Boehringer Ingelheim, Teijin Pharma, Takeda Pharmaceutical Company, Otsuka Pharmaceutical, Astellas Pharma, Pfizer Japan, Eisai. Stephen L. Hauser: received grant support from the US National Multiple Sclerosis Society and National Institute of Heath. Currently serves on the SAB of Symbiotix, Annexon, and Bionure. Jorge R. Oksenberg: received grant support from the US National Multiple Sclerosis Society and National Institute of Heath.
Abstract: P431
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Genetics/Epigenetics
Introduction: Parent-of-origin effect describes a phenotype that depends on whether a causative allele was inherited from the mother or the father.
Objectives: We aimed to investigate whether any parent-of-origin effects are observed in multiple sclerosis (MS) susceptibility.
Methods: We utilized a genome-wide single nucleotide polymorphism (SNP) dataset of 931 family trios (consisting of an affected child and both parents) of European origin. After strand phasing and SNP imputation, parent-of-origin effects were analyzed with the PREMIM/EMIM software. For each SNP, p values for maternal and paternal inheritance effects were assessed and those with p < 0.05 were evaluated.
Results: Out of 198 MS risk-associated non-MHC SNPs available on the chip, 24 had nominal statistically significant maternal parent-of-origin effects, whereas 21 had nominal paternal parent-of-origin effects. None of them passed the genome-wide significance threshold. However, in the EVI5 region in chromosome 1 where multiple independent MS risk-variants were identified, a SNP closest to GFI1 previously shown to be paternally expressed, displays paternal parent-of-origin effect for MS risk (rs58394161, p = 0.0099).
Conclusions: We analyzed parent-of-origin effects in MS and identified MS-associated variants with potential parent-of-origin effects on disease susceptibility. Parent-of-origin effects in regions with multiple independent MS variants may provide important clues on the functional mechanisms that contribute to MS risk and could partially explain the missing heritability in MS.
Disclosure: Noriko Isobe: received grant support from JSPS Kakenhi 18K07529, Japan Intractable Disease research Foundation, Japan Multiple Sclerosis Society, Mitsubishi Tanabe Pharma, Bayer Yakuhin, Ltd., and Japan Blood Products Organization. Andy Tsai: nothing to disclose. Stacy J Caillier: nothing to disclose.Adam Santaniello: nothing to disclose. Jun-ichi Kira: received rants, consultant fees, speaking fees and/or honoraria from AMED, Health, Labour and Welfare Sciences Research Grants, MEXT KAKENHI, JSPS KAKENHI, Novartis Pharma, Mitsubishi Tanabe Pharma, Boehringer Ingelheim, Teijin Pharma, Takeda Pharmaceutical Company, Otsuka Pharmaceutical, Astellas Pharma, Pfizer Japan, Eisai. Stephen L. Hauser: received grant support from the US National Multiple Sclerosis Society and National Institute of Heath. Currently serves on the SAB of Symbiotix, Annexon, and Bionure. Jorge R. Oksenberg: received grant support from the US National Multiple Sclerosis Society and National Institute of Heath.