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基于撒丁岛全基因组测序的全基因组关联分析为血红蛋白水平的调控提供了见解。

Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels.

作者信息

Danjou Fabrice, Zoledziewska Magdalena, Sidore Carlo, Steri Maristella, Busonero Fabio, Maschio Andrea, Mulas Antonella, Perseu Lucia, Barella Susanna, Porcu Eleonora, Pistis Giorgio, Pitzalis Maristella, Pala Mauro, Menzel Stephan, Metrustry Sarah, Spector Timothy D, Leoni Lidia, Angius Andrea, Uda Manuela, Moi Paolo, Thein Swee Lay, Galanello Renzo, Abecasis Gonçalo R, Schlessinger David, Sanna Serena, Cucca Francesco

机构信息

Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy.

Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.

出版信息

Nat Genet. 2015 Nov;47(11):1264-71. doi: 10.1038/ng.3307. Epub 2015 Sep 14.

DOI:10.1038/ng.3307
PMID:26366553
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4627580/
Abstract

We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.

摘要

我们报告了首次同时分析的A1、A2和胎儿血红蛋白水平的全基因组关联研究结果。通过对来自撒丁岛的一个大型普通人群队列进行高密度阵列基因分型和全基因组测序，我们在10个位点检测到了23个关联。其中5个信号是由于之前未检测到的位点上的变异所致：MPHOSPH9、PLTP - PCIF1、ZFPM1（FOG1）、NFIX和CCND3。在已知位点的信号中，有10个是新的先导变异，4个是新的独立信号。所有变异中有一半还显示出与不同血红蛋白的多效性关联，这进一步证实了一些检测到的关联，并确定了协调血红蛋白种类产生的特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa19/4627580/6479a1ae4a5a/emss-63149-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa19/4627580/713beed752ef/emss-63149-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa19/4627580/6479a1ae4a5a/emss-63149-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa19/4627580/713beed752ef/emss-63149-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa19/4627580/6479a1ae4a5a/emss-63149-f0002.jpg

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