荷兰人群特异性归因基因组鉴定出与胆固醇水平相关的ABCA6变体。
Genome of The Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels.
作者信息
van Leeuwen Elisabeth M, Karssen Lennart C, Deelen Joris, Isaacs Aaron, Medina-Gomez Carolina, Mbarek Hamdi, Kanterakis Alexandros, Trompet Stella, Postmus Iris, Verweij Niek, van Enckevort David J, Huffman Jennifer E, White Charles C, Feitosa Mary F, Bartz Traci M, Manichaikul Ani, Joshi Peter K, Peloso Gina M, Deelen Patrick, van Dijk Freerk, Willemsen Gonneke, de Geus Eco J, Milaneschi Yuri, Penninx Brenda W J H, Francioli Laurent C, Menelaou Androniki, Pulit Sara L, Rivadeneira Fernando, Hofman Albert, Oostra Ben A, Franco Oscar H, Mateo Leach Irene, Beekman Marian, de Craen Anton J M, Uh Hae-Won, Trochet Holly, Hocking Lynne J, Porteous David J, Sattar Naveed, Packard Chris J, Buckley Brendan M, Brody Jennifer A, Bis Joshua C, Rotter Jerome I, Mychaleckyj Josyf C, Campbell Harry, Duan Qing, Lange Leslie A, Wilson James F, Hayward Caroline, Polasek Ozren, Vitart Veronique, Rudan Igor, Wright Alan F, Rich Stephen S, Psaty Bruce M, Borecki Ingrid B, Kearney Patricia M, Stott David J, Adrienne Cupples L, Jukema J Wouter, van der Harst Pim, Sijbrands Eric J, Hottenga Jouke-Jan, Uitterlinden Andre G, Swertz Morris A, van Ommen Gert-Jan B, de Bakker Paul I W, Eline Slagboom P, Boomsma Dorret I, Wijmenga Cisca, van Duijn Cornelia M
机构信息
Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
出版信息
Nat Commun. 2015 Mar 9;6:6065. doi: 10.1038/ncomms7065.
Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of The Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value <6.61 × 10(-4)), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C=0.135, βTC=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR.
与血脂水平相关的变异可能具有人群特异性。为了识别与该表型相关的低频变异，可以使用人群特异性参考面板。在此，我们利用荷兰基因组计划创建的人群特异性参考面板对九个大型荷兰生物样本库（约35000个样本）进行基因填充，并对血脂水平进行关联测试。我们报告在四个基因座发现了五个新的关联（P值<6.61×10⁻⁴），包括ABCA6中的一个罕见错义变异（rs77542162，p.Cys1359Arg，频率0.034），预计该变异有害。该ABCA6变异在荷兰人群中的频率增加了3.65倍，其效应（βLDL-C = 0.135，βTC = 0.140）估计与在知名脂质基因（如LDLR）中的单变异观察到的效应非常相似。
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