Properties of local interactions and their potential value in complementing genome-wide association studies.
Properties of local interactions and their potential value in complementing genome-wide association studies.
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局部相互作用的特性及其在补充全基因组关联研究中的潜在价值。
DOI：
10.1371/journal.pone.0071203
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Haley CS
中科院分区：
文献类型：
--
作者：
Wei W;Gyenesei A;Semple CA;Haley CS
邻近SNP之间的局部相互作用被假设能够通过单倍型效应捕获全基因组关联研究（GWAS）中缺失的变体，但尚未被彻底探索。我们使用了一种新的高通量分析工具，通过全成对基因组扫描和常规GWAS，在1966年北方芬兰出生队列（NFBC1966）和社区动脉粥样硬化风险研究队列（ARIC）中对舒张压和收缩压以及六种代谢特征进行了研究。在ARIC中检测到PLEKHA7与收缩压之间的全基因组显著相互作用。（已知的血压GWAS位点）和GPR180（其在血管重塑中起作用），以及甘油三酯作为11q23.3区域内的局部相互作用（在NFBC1966中显著复制），其显著地含有有助于甘油三酯水平的几个基因座（BUD13、ZNF 259和APOA 5）。在11q23.3区域内的局部相互作用的测试条件的顶部GWAS信号表明存在两个独立的功能变体，每个支持的证据，其在基因调控中的作用。局部相互作用捕获了本研究中发现的9个额外GWAS基因座（3个显着重复）和来自之前GWAS的73个基因座（8个性状中的24个和相关性状中的49个）。我们的结论是，检测本地的相互作用需要足够的SNP覆盖的基因组，这种相互作用只可能是检测到低连锁不平衡的SNP之间。分析局部相互作用是对GWAS的潜在有价值的补充，可以为复杂性状变异的生物学基础提供新的见解。
Local interactions between neighbouring SNPs are hypothesized to be able to capture variants missing from genome-wide association studies (GWAS) via haplotype effects but have not been thoroughly explored. We have used a new high-throughput analysis tool to probe this underexplored area through full pair-wise genome scans and conventional GWAS in diastolic and systolic blood pressure and six metabolic traits in the Northern Finland Birth Cohort 1966 (NFBC1966) and the Atherosclerosis Risk in Communities study cohort (ARIC). Genome-wide significant interactions were detected in ARIC for systolic blood pressure between PLEKHA7 (a known GWAS locus for blood pressure) and GPR180 (which plays a role in vascular remodelling), and also for triglycerides as local interactions within the 11q23.3 region (replicated significantly in NFBC1966), which notably harbours several loci (BUD13, ZNF259 and APOA5) contributing to triglyceride levels. Tests of the local interactions within the 11q23.3 region conditional on the top GWAS signal suggested the presence of two independent functional variants, each with supportive evidence for their roles in gene regulation. Local interactions captured 9 additional GWAS loci identified in this study (3 significantly replicated) and 73 from previous GWAS (24 in the eight traits and 49 in related traits). We conclude that the detection of local interactions requires adequate SNP coverage of the genome and that such interactions are only likely to be detectable between SNPs in low linkage disequilibrium. Analysing local interactions is a potentially valuable complement to GWAS and can provide new insights into the biology underlying variation in complex traits.
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影响因子：
30.8
作者：
Kettunen, Johannes;Tukiainen, Taru;Sarin, Antti-Pekka;Ortega-Alonso, Alfredo;Tikkanen, Emmi;Lyytikainen, Leo-Pekka;Kangas, Antti J.;Soininen, Pasi;Wuertz, Peter;Silander, Kaisa;Dick, Danielle M.;Rose, Richard J.;Savolainen, Markku J.;Viikari, Jorma;Kahonen, Mika;Lehtimaki, Terho;Pietilainen, Kirsi H.;Inouye, Michael;McCarthy, Mark I.;Jula, Antti;Eriksson, Johan;Raitakari, Olli T.;Salomaa, Veikko;Kaprio, Jaakko;Jarvelin, Marjo-Riitta;Peltonen, Leena;Perola, Markus;Freimer, Nelson B.;Ala-Korpela, Mika;Palotie, Aarno;Ripatti, Samuli
通讯作者：
Ripatti, Samuli
DOI：
10.1038/nrg2579
发表时间：
2009-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Cordell HJ
通讯作者：
Cordell HJ
影响因子：
14.9
作者：
Gyenesei A;Moody J;Laiho A;Semple CA;Haley CS;Wei WH
通讯作者：
Wei WH
影响因子：
37.8
作者：
Dehghan A;Dupuis J;Barbalic M;Bis JC;Eiriksdottir G;Lu C;Pellikka N;Wallaschofski H;Kettunen J;Henneman P;Baumert J;Strachan DP;Fuchsberger C;Vitart V;Wilson JF;Paré G;Naitza S;Rudock ME;Surakka I;de Geus EJ;Alizadeh BZ;Guralnik J;Shuldiner A;Tanaka T;Zee RY;Schnabel RB;Nambi V;Kavousi M;Ripatti S;Nauck M;Smith NL;Smith AV;Sundvall J;Scheet P;Liu Y;Ruokonen A;Rose LM;Larson MG;Hoogeveen RC;Freimer NB;Teumer A;Tracy RP;Launer LJ;Buring JE;Yamamoto JF;Folsom AR;Sijbrands EJ;Pankow J;Elliott P;Keaney JF;Sun W;Sarin AP;Fontes JD;Badola S;Astor BC;Hofman A;Pouta A;Werdan K;Greiser KH;Kuss O;Meyer zu Schwabedissen HE;Thiery J;Jamshidi Y;Nolte IM;Soranzo N;Spector TD;Völzke H;Parker AN;Aspelund T;Bates D;Young L;Tsui K;Siscovick DS;Guo X;Rotter JI;Uda M;Schlessinger D;Rudan I;Hicks AA;Penninx BW;Thorand B;Gieger C;Coresh J;Willemsen G;Harris TB;Uitterlinden AG;Järvelin MR;Rice K;Radke D;Salomaa V;Willems van Dijk K;Boerwinkle E;Vasan RS;Ferrucci L;Gibson QD;Bandinelli S;Snieder H;Boomsma DI;Xiao X;Campbell H;Hayward C;Pramstaller PP;van Duijn CM;Peltonen L;Psaty BM;Gudnason V;Ridker PM;Homuth G;Koenig W;Ballantyne CM;Witteman JC;Benjamin EJ;Perola M;Chasman DI
通讯作者：
Chasman DI
影响因子：
4.5
作者：
Ma L;Brautbar A;Boerwinkle E;Sing CF;Clark AG;Keinan A
通讯作者：
Keinan A