Parental origin of sequence variants associated with complex diseases

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through gen...

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Bibliographic Details
Published in:Nature
Main Authors: Kong, Augustine, Steinthorsdottir, Valgerdur, Masson, Gisli, Thorleifsson, Gudmar, Sulem, Patrick, Besenbacher, Soren, Jonasdottir, Aslaug, Sigurdsson, Asgeir, Kristinsson, Kari Th, Jonasdottir, Adalbjorg, Frigge, Michael L, Gylfason, Arnaldur, Olason, Pall I, Gudjonsson, Sigurjon A, Sverrisson, Sverrir, Stacey, Simon N, Sigurgeirsson, Bardur, Benediktsdottir, Kristrun R, Sigurdsson, Helgi, Jonsson, Thorvaldur, Benediktsson, Rafn, Olafsson, Jon H, Johannsson, Oskar Th, Hreidarsson, Astradur B, Sigurdsson, Gunnar, Ferguson-Smith, Anne C, Gudbjartsson, Daniel F, Thorsteinsdottir, Unnur, Stefansson, Kari
Other Authors: deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland. kong@decode.is
Format: Article in Journal/Newspaper
Language:English
Published: Nature Publishing Group 2011
Subjects:
Alleles
Binding Sites
Breast Neoplasms
Carcinoma
Basal Cell
Chromosomes
Human
Pair 11
Pair 7
DNA Methylation
Diabetes Mellitus
Type 2
Fathers
Female
Genetic Predisposition to Disease
Genome
Genomic Imprinting
Haplotypes
Humans
Iceland
Male
Mothers
Pedigree
Polymorphism
Single Nucleotide
Repressor Proteins
Online Access:http://hdl.handle.net/2336/125157
https://doi.org/10.1038/nature08625
Description
Summary:To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site. info:eu-repo/grantAgreement/EC/FP7/218071

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