期刊
NATURE
卷 462, 期 7275, 页码 868-U59出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature08625
关键词
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资金
- FP7-MC-IAPP [218071]
- MRC [G9723500, MC_U106179474, MC_U127592696] Funding Source: UKRI
- Medical Research Council [MC_U127592696, G9723500, MC_U106179474, MC_U106179471] Funding Source: researchfish
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.
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