Kochunov Peter, Glahn David, Lancaster Jack, Winkler Anderson, Kent Jack W, Olvera Rene L, Cole Shelley A, Dyer Thomas D, Almasy Laura, Duggirala Ravi, Fox Peter T, Blangero John
Dip ABMP, Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284, USA.
Stroke. 2010 Oct;41(10):2137-42. doi: 10.1161/STROKEAHA.110.590943. Epub 2010 Aug 19.
The volume of T2-hyperintense white matter (HWM) is an important neuroimaging marker of cerebral integrity with a demonstrated high heritability. Pathophysiology studies have shown that the regional, ependymal, and subcortical HWM lesions are associated with elevated arterial pulse pressure and arterial blood pressure (BP), respectively. We performed bivariate, whole-genome linkage analyses for HWM volumes and BP measurements to identify chromosomal regions that contribute jointly to both traits in a population of healthy Mexican Americans. Our aims were to localize novel quantitative trait loci acting pleiotropically on these phenotypes and to replicate previous genetic findings on whole brain HWM volume and BP measurements.
BP measurements and volumes of whole-brain (WB), subcortical, and ependymal HWM lesions, measured from high-resolution (1 mm(3)) 3-dimensional fluid-attenuated inversion recovery images, served as focal quantitative phenotypes. Data were collected from 357 (218 females; mean age=47.9±13.2 years) members of large extended families who participated in the San Antonio Family Heart Study.
Bivariate genomewide linkage analyses localized a significant quantitative trait locus influencing WB and regional (ependymal) HWM volumes and pulse pressure and systolic BP to chromosomal location 1q24 between markers D1S196 and D1S1619. Several other chromosomal regions (1q42, 10q24-q26, and 15q26) exhibited suggestive linkages. The results of the post hoc analyses that excluded 55 subjects taking antihypertensive medication showed no substantive differences from the results obtained in the full cohort.
This study confirms several previously observed quantitative trait loci influencing BP and cerebral integrity and identifies a novel significant quantitative trait locus at chromosome 1q24. The genetic results strongly support a role for pleiotropically acting genes jointly influencing BP and cerebral white matter integrity.
T2高信号白质（HWM）体积是脑完整性的重要神经影像学标志物，具有较高的遗传度。病理生理学研究表明，区域性、室管膜下和皮质下HWM病变分别与动脉脉压和动脉血压（BP）升高有关。我们对HWM体积和BP测量值进行了双变量全基因组连锁分析，以确定在健康墨西哥裔美国人中对这两个性状均有影响的染色体区域。我们的目的是定位对这些表型具有多效性作用的新数量性状基因座，并重复先前关于全脑HWM体积和BP测量的遗传研究结果。
从高分辨率（1 mm³）三维液体衰减反转恢复图像测量的BP值以及全脑（WB）、皮质下和室管膜下HWM病变体积作为重点数量性状表型。数据收集自参与圣安东尼奥家族心脏研究的357名（218名女性；平均年龄 = 47.9±13.2岁）大家庭成员。
双变量全基因组连锁分析将一个影响WB和区域（室管膜下）HWM体积以及脉压和收缩压BP的显著数量性状基因座定位到标记D1S196和D1S1619之间的染色体位置1q24。其他几个染色体区域（1q42、10q24 - q26和15q26）显示出提示性连锁。排除55名服用抗高血压药物受试者的事后分析结果与全队列获得的结果无实质性差异。
本研究证实了几个先前观察到的影响BP和脑完整性的数量性状基因座，并在染色体1q24处鉴定出一个新的显著数量性状基因座。遗传结果有力地支持了多效性作用基因在共同影响BP和脑白质完整性方面的作用。
