基因序列变异与人类特征之间的很多联系已在“基因组关联研究”（GWAS）中被发现，但这些研究大都将母方和父方等位基因当成是可相互转变的，所以我们对来源于父方的序列变异怎样影响表现型知之甚少。
一种将系谱分析与长距定相结合起来的新的GWAS方法，可以确定多数定位基因的父方来源，对超过38,000名冰岛人的基因型所做的一项调查就表明了这一点。以前被发现与复杂疾病相关的五个单核苷酸变异体（一个与乳腺癌相关，一个与基底细胞癌相关，三个与2-型糖尿病相关），被发现取决于父方来源。在遗传自母方时具有保护性的一个新的变异体若遗传自父方，对糖尿病风险的贡献则仅次于基因TCF7L2变异体的贡献。（生物谷Bioon.com）
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生物谷推荐原始出处：
Nature 462, 868-874 (17 December 2009) | doi:10.1038/nature08625
Parental origin of sequence variants associated with complex diseases
Augustine Kong1, Valgerdur Steinthorsdottir1,98, Gisli Masson1,98, Gudmar Thorleifsson1,98, Patrick Sulem1, Soren Besenbacher1, Aslaug Jonasdottir1, Asgeir Sigurdsson1, Kari Th. Kristinsson1, Adalbjorg Jonasdottir1, Michael L. Frigge1, Arnaldur Gylfason1, Pall I. Olason1, Sigurjon A. Gudjonsson1, Sverrir Sverrisson1, Simon N. Stacey1, Bardur Sigurgeirsson2, Kristrun R. Benediktsdottir3, Helgi Sigurdsson4, Thorvaldur Jonsson5, Rafn Benediktsson6, Jon H. Olafsson2, Oskar Th. Johannsson4, Astradur B. Hreidarsson6, Gunnar Sigurdsson6, DIAGRAM Consortium, Anne C. Ferguson-Smith7, Daniel F. Gudbjartsson1, Unnur Thorsteinsdottir1,8 & Kari Stefansson1,8
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.
