Admixture mapping in the Hispanic Community Health Study/Study of Latinos reveals regions of genetic associations with blood pressure traits.

Admixture mapping in the Hispanic Community Health Study/Study of Latinos reveals regions of genetic associations with blood pressure traits.
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DOI:
10.1371/journal.pone.0188400
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
Franceschini N
Franceschini N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sofer T;Baier LJ;Browning SR;Thornton TA;Talavera GA;Wassertheil-Smoller S;Daviglus ML;Hanson R;Kobes S;Cooper RS;Cai J;Levy D;Reiner AP;Franceschini N

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混合作图可以通过估计当地祖先等位基因计数和感兴趣的性状之间的关联,来检测混合群体中的遗传关联区域,例如拉美裔/拉丁裔。我们对来自西班牙裔社区健康研究/拉丁裔研究(HCHS/SOL)的12,116名参与者的血压特征进行了混合映射,包括收缩压和舒张压(SBP,DBP)、平均动脉压(MAP)和脉压(PP)。拉美裔/拉丁裔有三个主要的祖先群体(欧洲人、非洲人和美洲印第安人),我们分别测试了每一个人的基因组中的当地祖先间隔。我们在全基因组混合作图水平上确定了与血压性状显著相关的四个区域。6p21.31美洲印第安人祖先关联区有多个已知关联,但没有一个解释混合映射信号。我们确定了完全解释这一信号的变种。在皮马印第安人的复制测试中,其中一个变异的p值分别为0.02(MAP)和0.04(SBP)。11q13.4美洲印第安人血统关联区域跨越了先前在一项关于血压(BP)特征和维生素D途径中的变异的有针对性的关联研究中报告的变异(p值=0.001)。没有复制证据支持在已确定的17q25.3美洲印第安人祖先协会区域中存在关联。对于6p12.3上与非洲血统相关的区域,我们没有发现任何驱动该关联的候选变异。它可能是由罕见的变种驱动的。全基因组序列数据可能是精细定位这些关联信号所必需的,这可能导致不同种群之间BP特征的差异。
Admixture mapping can be used to detect genetic association regions in admixed populations, such as Hispanics/Latinos, by estimating associations between local ancestry allele counts and the trait of interest. We performed admixture mapping of the blood pressure traits systolic and diastolic blood pressure (SBP, DBP), mean arterial pressure (MAP), and pulse pressure (PP), in a dataset of 12,116 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hispanics/Latinos have three predominant ancestral populations (European, African, and Amerindian), for each of which we separately tested local ancestry intervals across the genome. We identified four regions that were significantly associated with a blood pressure trait at the genome-wide admixture mapping level. A 6p21.31 Amerindian ancestry association region has multiple known associations, but none explained the admixture mapping signal. We identified variants that completely explained this signal. One of these variants had p-values of 0.02 (MAP) and 0.04 (SBP) in replication testing in Pima Indians. A 11q13.4 Amerindian ancestry association region spans a variant that was previously reported (p-value = 0.001) in a targeted association study of Blood Pressure (BP) traits and variants in the vitamin D pathway. There was no replication evidence supporting an association in the identified 17q25.3 Amerindian ancestry association region. For a region on 6p12.3, associated with African ancestry, we did not identify any candidate variants driving the association. It may be driven by rare variants. Whole genome sequence data may be necessary to fine map these association signals, which may contribute to disparities in BP traits between diverse populations.
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发表时间: 2016-10
期刊: Nature genetics
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DOI: 10.1086/302061
发表时间: 1998-10-01
影响因子: 9.8
作者:
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通讯作者: Knowler, WC