Five blood pressure loci identified by an updated genome-wide linkage scan: meta-analysis of the Family Blood Pressure Program.
Five blood pressure loci identified by an updated genome-wide linkage scan: meta-analysis of the Family Blood Pressure Program.
复制标题
通过更新的全基因组连锁扫描识别出五个血压位点：家庭血压计划的荟萃分析。
DOI：
10.1038/ajh.2010.238
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发表时间：
2011
影响因子：
3.2
通讯作者：
Coope
中科院分区：
文献类型：
--
作者：
Simino,Jeannette;Shi,Gang;Kume,Rezart;Schwander,Karen;Province,MichaelA;Gu,CCharles;Kardia,Sharon;Chakravarti,Aravinda;Ehret,Georg;Olshen,RichardA;Turner,StephenT;Ho,Low-Tone;Zhu,Xiaofeng;Jaquish,Cashell;Paltoo,Dina;Coope
背景先前曾报道过家庭血压计划（FBPP）中血压的初步全基因组连锁分析。我们利用最终合并的 FBPP 数据集的力量和种族多样性来识别新的血压位点，从而增强包含对血压水平和高血压影响较大的不太常见变异的基因的定位。方法我们使用 4,226 名非洲裔美国人、2,154 名亚洲人、 4,229 名白人和 2,435 名墨西哥裔美国人参与者（总 N = 13,044）。方差分量模型适合测量的（原始）血压水平和两种类型的抗高血压药物调整按种族和网络定义的 10 个亚组中的每一个亚组中的血压表型。使用改进的 Fisher 方法组合 10 个亚组中每个连锁标记的 P 值。结果基于显着连锁证据（由比值对数 (lod) 评分≥3 定义），在染色体 6p22.3、8q23.1、20q13.12、21q21.1 和 21q21.3 上检测到 5 个数量性状位点 (QTL)。 荟萃分析且在至少 2 个由网络和种族定义的亚组中 lod 分数≥1。染色体 8q23.1 位点得到了亚洲人、高加索人和墨西哥裔美国人特定荟萃分析的支持。 结论 报告的新 QTL 证明了新候选基因研究的合理性。它们可能有助于支持属于这些 QTL 区域的全基因组关联研究 (GWAS) 的结果，但未能实现全基因组显着性。American Journal of Hypertensionadvance 在线出版物 2010 年 12 月 9 日；doi:10.1038/ajh.2010.238
BackgroundA preliminary genome-wide linkage analysis of blood pressure in the Family Blood Pressure Program (FBPP) was reported previously. We harnessed the power and ethnic diversity of the final pooled FBPP dataset to identify novel loci for blood pressure thereby enhancing localization of genes containing less common variants with large effects on blood pressure levels and hypertension.MethodsWe performed one overall and 4 race-specific meta-analyses of genome-wide blood pressure linkage scans using data on 4,226African-American, 2,154 Asian, 4,229 Caucasian, and 2,435 Mexican- American participants (total N = 13,044). Variance components models were fit to measured (raw) blood pressure levels and two types of antihypertensive medication adjusted blood pressure phenotypes within each of 10 subgroups defined by race and network. A modified Fisher’s method was used to combine the P values for each linkage marker across the 10 subgroups.ResultsFive quantitative trait loci (QTLs) were detected on chromosomes 6p22.3, 8q23.1, 20q13.12, 21q21.1, and 21q21.3 based on significant linkage evidence (defined by logarithm of odds (lod) score ≥3) in at least one meta-analysis and lod scores ≥1 in at least 2 subgroups defined by network and race. The chromosome 8q23.1 locus was supported by Asian-, Caucasian-, and Mexican-American-specific meta-analyses.ConclusionsThe new QTLs reported justify new candidate gene studies. They may help support results from genome-wide association studies (GWAS) that fall in these QTL regions but fail to achieve the genome-wide significance.American Journal of Hypertensionadvance online publication 9 December 2010;doi:10.1038/ajh.2010.238