Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels.
Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels.
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DOI：
10.1038/ng.3307
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发表时间：
2015-11
期刊：
影响因子：
30.8
通讯作者：
Cucca F
中科院分区：
文献类型：
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作者：
Danjou F;Zoledziewska M;Sidore C;Steri M;Busonero F;Maschio A;Mulas A;Perseu L;Barella S;Porcu E;Pistis G;Pitzalis M;Pala M;Menzel S;Metrustry S;Spector TD;Leoni L;Angius A;Uda M;Moi P;Thein SL;Galanello R;Abecasis GR;Schlessinger D;Sanna S;Cucca F
我们报告了首次同时分析的 A1、A2 和胎儿血红蛋白水平的 GWAS 结果。在撒丁岛的一个大型普通人群队列中整合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 23 个关联。其中五个是由于以前未检测到的基因座的变异引起的：MPHOSPH9、PLTP-PCIF1、FOG1、NFIX 和 CCND3。在已知基因座的信号中，10 个是新的先导变异，4 个是新的独立信号。所有变异中的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揭示了协调血红蛋白物种产生的特征。
We report GWAS 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 are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, FOG1, NFIX, and CCND3. Among those at known loci, 10 are new lead variants and 4 are novel independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and revealed features of coordinated hemoglobin species production.