基因序列變異與人類特征之間的很多聯(lián)系已在“基因組關(guān)聯(lián)研究”（GWAS）中被發(fā)現(xiàn),，但這些研究大都將母方和父方等位基因當(dāng)成是可相互轉(zhuǎn)變的，所以我們對來源于父方的序列變異怎樣影響表現(xiàn)型知之甚少。
一種將系譜分析與長距定相結(jié)合起來的新的GWAS方法,，可以確定多數(shù)定位基因的父方來源，對超過38,000名冰島人的基因型所做的一項(xiàng)調(diào)查就表明了這一點(diǎn),。以前被發(fā)現(xiàn)與復(fù)雜疾病相關(guān)的五個(gè)單核苷酸變異體（一個(gè)與乳腺癌相關(guān),，一個(gè)與基底細(xì)胞癌相關(guān)，三個(gè)與2-型糖尿病相關(guān)）,，被發(fā)現(xiàn)取決于父方來源,。在遺傳自母方時(shí)具有保護(hù)性的一個(gè)新的變異體若遺傳自父方，對糖尿病風(fēng)險(xiǎn)的貢獻(xiàn)則僅次于基因TCF7L2變異體的貢獻(xiàn),。（生物谷Bioon.com）
全基因組關(guān)聯(lián)研究：
Nature Genetics：全基因組關(guān)聯(lián)研究發(fā)現(xiàn)帕金森氏癥易感基因
Nature Methods：小鼠全基因組關(guān)聯(lián)研究(GWAS)芯片開發(fā)成功,！
Nature Genetics：首個(gè)種族特異性結(jié)腸癌基因變異確定
PLoS Genet：全基因組關(guān)聯(lián)研究或能提高疾病預(yù)測的準(zhǔn)確性
Nature Genetics：首次發(fā)現(xiàn)與睪丸癌有關(guān)基因
Nature Genetics：發(fā)現(xiàn)老年癡呆癥相關(guān)三個(gè)基因
Nature Genetics ：發(fā)現(xiàn)克羅恩氏病21種新遺傳風(fēng)險(xiǎn)因子
Nature Genetics：多痣者易患黑色素瘤
Nature：找到自閉癥易感基因
Nature Genetics：發(fā)現(xiàn)胰島素抗性變異基因
PLoS Genet：確定出與兒童哮喘相關(guān)的基因區(qū)域
Nature Genetics：亞裔人群乙肝易感基因變異
生物谷推薦原始出處：
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.
