Review: a meta-analysis of GWAS and age-associated diseases.
Review: a meta-analysis of GWAS and age-associated diseases.
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DOI：
10.1111/j.1474-9726.2012.00871.x
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发表时间：
2012-10
期刊：
影响因子：
7.8
通讯作者：
Sharpless NE
中科院分区：
文献类型：
--
作者：
Jeck WR;Siebold AP;Sharpless NE
全基因组关联研究 (GWAS) 通过识别与复杂表型的因果变异相关的单核苷酸多态性 (SNP)，提供了一种了解性状遗传基础的无偏见方法。 GWAS 已鉴定出许多与许多重要人类疾病相关的易感性 SNP，包括与衰老相关的疾病。为了了解对年龄相关疾病（即“健康”）的广泛抵抗力的遗传学，我们对人类 GWAS 进行了荟萃分析。为此，我们编制了 372 个 GWAS，确定了 1,775 个对 105 种独特疾病的易感性 SNP，并利用这些 SNP 创建了疾病易感性的基因组图谱。该图谱的构建方法是将基因组划分为 200 kb 的“bins”，并根据基因组位置将 1,775 个易感性 SNP 映射到 bins。对这些数据的调查揭示了基因组内疾病关联的显着异质性，92% 的 bin 缺乏与疾病相关的 SNP。相比之下，10 个箱 (0.06%) 对多种疾病的易感性显着富集 (p<0.05)，其中 5 个箱形成两个高度显着的疾病关联峰 (p<0.0001)。这些峰映射到 6p21 上的主要组织相容性 (MHC) 基因座和 9p21.3 上的 INK4/ARF (CDKN2a/b) 肿瘤抑制基因座。令人兴奋的是，所有 10 个显着富集的 bin 都包含与炎症或细胞衰老途径相关的基因，并且衰老调节因子附近的 SNP 特别与衰老疾病（例如癌症、动脉粥样硬化、2 型糖尿病、青光眼）相关。该分析表明，免疫和细胞衰老调节中的种系遗传异质性影响人类的健康寿命。
Genome-Wide Association studies (GWAS) offer an unbiased means to understand the genetic basis of traits by identifying single nucleotide polymorphisms (SNPs) linked to causal variants of complex phenotypes. GWAS have identified a host of susceptibility SNPs associated with many important human diseases, including diseases associated with aging. In an effort to understand the genetics of broad resistance to age-associated diseases (i.e. ‘wellness’), we performed a meta-analysis of human GWAS. Toward that end, we compiled 372 GWAS that identified 1,775 susceptibility SNPs to 105 unique diseases and used these SNPs to create a genomic landscape of disease susceptibility. This map was constructed by partitioning the genome into 200 kb ‘bins’ and mapping the 1,775 susceptibility SNPs to bins based on their genomic location. Investigation of these data revealed significant heterogeneity of disease association within the genome, with 92% of bins devoid of disease-associated SNPs. In contrast, 10 bins (0.06%) were significantly (p<0.05) enriched for susceptibility to multiple diseases, 5 of which formed two highly significant peaks of disease association (p<0.0001). These peaks mapped to the Major Histocompatibility (MHC) locus on 6p21 and the INK4/ARF (CDKN2a/b) tumor suppressor locus on 9p21.3. Provocatively, all 10 significantly enriched bins contained genes linked to either inflammation or cellular senescence pathways, and SNPs near regulators of senescence were particularly associated with disease of aging (e.g. cancer, atherosclerosis, type 2 diabetes, glaucoma). This analysis suggests that germline genetic heterogeneity in the regulation of immunity and cellular senescence influences the human health span.
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影响因子：
30.8
作者：
McKay, James D.;Hung, Rayjean J.;Gaborieau, Valerie;Boffetta, Paolo;Chabrier, Amelie;Byrnes, Graham;Zaridze, David;Mukeria, Anush;Szeszenia-Dabrowska, Neonilia;Lissowska, Jolanta;Rudnai, Peter;Fabianova, Eleonora;Mates, Dana;Bencko, Vladimir;Foretova, Lenka;Janout, Vladimir;McLaughlin, John;Shepherd, Frances;Montpetit, Alexandre;Narod, Steven;Krokan, Hans E.;Skorpen, Frank;Elvestad, Maiken Bratt;Vatten, Lars;Njolstad, Inger;Axelsson, Tomas;Chen, Chu;Goodman, Gary;Barnett, Matt;Loomis, Melissa M.;Lubinski, Jan;Matyjasik, Joanna;Lener, Marcin;Oszutowska, Dorota;Field, John;Liloglou, Triantafillos;Xinarianos, George;Cassidy, Adrian;Zelenika, Diana;Boland, Anne;Delepine, Marc;Foglio, Mario;Lechner, Doris;Matsuda, Fumihiko;Blanche, Helene;Gut, Ivo;Heath, Simon;Lathrop, Mark;Brennan, Paul
通讯作者：
Brennan, Paul
影响因子：
7.8
作者：
Pawlikowska L;Hu D;Huntsman S;Sung A;Chu C;Chen J;Joyner AH;Schork NJ;Hsueh WC;Reiner AP;Psaty BM;Atzmon G;Barzilai N;Cummings SR;Browner WS;Kwok PY;Ziv E;Study of Osteoporotic Fractures
通讯作者：
Study of Osteoporotic Fractures
DOI：
10.1073/pnas.0705467105
发表时间：
2008-03-04
影响因子：
11.1
作者：
Suh, Yousin;Atzmon, Gil;Cohen, Pinchas
通讯作者：
Cohen, Pinchas
影响因子：
5
作者：
Jorgensen, Timothy J.;Ruczinski, Ingo;Alberg, Anthony J.
通讯作者：
Alberg, Anthony J.
DOI：
10.1073/pnas.0909307106
发表时间：
2009-11-03
影响因子：
11.1
作者：
Rioux, John D.;Goyette, Philippe;Hauser, Stephen L.
通讯作者：
Hauser, Stephen L.