Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.
Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.
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DOI：
10.1038/ng.271
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发表时间：
2009-01
期刊：
影响因子：
30.8
通讯作者：
Peltonen, Leena
中科院分区：
文献类型：
--
作者：
Sabatti, Chiara;Service, Susan K.;Hartikainen, Anna-Liisa;Pouta, Anneli;Ripatti, Samuli;Brodsky, Jae;Jones, Chris G.;Zaitlen, Noah A.;Varilo, Teppo;Kaakinen, Marika;Sovio, Ulla;Ruokonen, Aimo;Laitinen, Jaana;Jakkula, Eveliina;Coin, Lachlan;Hoggart, Clive;Collins, Andrew;Turunen, Hannu;Gabriel, Stacey;Elliot, Paul;McCarthy, Mark I.;Daly, Mark J.;Jarvelin, Marjo-Riitta;Freimer, Nelson B.;Peltonen, Leena
纵向出生队列的全基因组关联研究（GWAS）可以联合研究环境和遗传对复杂性状的影响。我们报告了 1966 年芬兰北部出生队列 (NFBC1966) 九个定量代谢特征（甘油三酯、高密度脂蛋白、低密度脂蛋白、葡萄糖、胰岛素、C 反应蛋白、体重指数以及收缩压和舒张压）的 GWAS 结果，这些队列来自芬兰基因最孤立的地区。我们复制了大多数先前报道的这些性状的关联，并确定了九个新的关联，其中几个突出了具有代谢功能的基因：高密度脂蛋白与NR1H3（LXRA）、低密度脂蛋白与AR和FADS1-FADS2、葡萄糖与MTNR1B以及胰岛素与PANK1。在调整体重指数结果后，出现了其中两个新的关联。基因-环境相互作用分析表明存在其他关联，这需要在更大的样本中进行验证。目前确定的位点以及量化的环境暴露几乎无法解释 NFBC1966 中的性状变异。观察到的低密度脂蛋白与 AR 中罕见变异之间的关联表明，这样的队列具有识别与常见、低影响和罕见、高影响数量性状位点的关联的潜力。
Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.
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与人类血液低密度脂蛋白胆固醇、高密度脂蛋白胆固醇或甘油三酯相关的六个新位点。
影响因子：
30.8
作者：
Kathiresan, Sekar;Melander, Olle;Guiducci, Candace;Surti, Aarti;Burtt, Noel P.;Rieder, Mark J.;Cooper, Gregory M.;Roos, Charlotta;Voight, Benjamin F.;Havulinna, Aki S.;Wahlstrand, Bjorn;Hedner, Thomas;Corella, Dolores;Tai, E. Shyong;Ordovas, Jose M.;Berglund, Goran;Vartiainen, Erkki;Jousilahti, Pekka;Hedblad, Bo;Taskinen, Marja-Riitta;Newton-Cheh, Christopher;Salomaa, Veikko;Peltonen, Leena;Groop, Leif;Altshuler, David M.;Orho-Melander, Marju
通讯作者：
Orho-Melander, Marju
影响因子：
2.1
作者：
Bacanu, SA;Devlin, B;Roeder, K
通讯作者：
Roeder, K
影响因子：
158.5
作者：
Barker, DJP;Osmond, C;Eriksson, JG
通讯作者：
Eriksson, JG
影响因子：
9.8
作者：
Lasky-Su, Jessica;Lyon, Helen N.;Lange, Christoph
通讯作者：
Lange, Christoph
影响因子：
2.1
作者：
Klei, Lambertus;Luca, Diana;Roeder, Kathryn
通讯作者：
Roeder, Kathryn