Atwood L D, Samollow P B, Hixson J E, Stern M P, MacCluer J W
Division of Epidemiology and Institute of Human Genetics, University of Minnesota, Minneapolis 55454-1015, USA.
Genet Epidemiol. 2001 Apr;20(3):373-82. doi: 10.1002/gepi.7.
The genetic mechanisms that control variation in blood pressure level are largely unknown. One of the first steps in understanding those mechanisms is the localization of the genes that have a significant effect on blood pressure. We performed genome scans of systolic (SBP) and diastolic blood pressure (DBP) on a population-based sample of families in the San Antonio Family Heart Study. A likelihood-based Mendelian model incorporating genotype-specific effects of sex, age, age(2), BMI, and blood pressure (SBP or DBP, as appropriate) as covariates was used to perform two-point lodscore (Z) linkage on 399 polymorphic markers. Results showed that the genotype-specific covariate effects were highly significant for both SBP and DBP. Linkage results showed that a quantitative trait locus (QTL) influencing DBP was significantly linked to D2S1790 (Z = 3.92, theta = 0.00) and showed suggestive linkage to D8S373 (Z = 1.92, theta = 0.00). A QTL influencing SBP showed suggestive linkage to D21S1440 (Z = 2.82, theta = 0.00) and D18S844 (Z = 2.09, theta = 0.11). Without the genotype-specific effects in the model, the linkage to D2S1790 was not even suggestive (Z = 1.33, theta = 0.09); thus genotype-specific modeling was crucial in detecting this linkage. A comparison with linkage studies based in other populations showed that the significant linkage to D2S1790 has been replicated at the same marker in the Quebec Family Study. The replicated significant linkage at D2S1790 may begin to establish the locations of the genes that significantly affect blood pressure across several human ethnic groups.
控制血压水平变异的遗传机制在很大程度上尚不清楚。理解这些机制的首要步骤之一是定位对血压有显著影响的基因。我们在圣安东尼奥家族心脏研究中基于人群的家庭样本上进行了收缩压（SBP）和舒张压（DBP）的全基因组扫描。使用了一个基于似然的孟德尔模型，该模型将性别、年龄、年龄²、体重指数（BMI）以及血压（适当时为SBP或DBP）的基因型特异性效应作为协变量，对399个多态性标记进行两点连锁对数记分（Z）分析。结果表明，基因型特异性协变量效应对于SBP和DBP均具有高度显著性。连锁分析结果显示，一个影响DBP的数量性状位点（QTL）与D2S1790显著连锁（Z = 3.92，θ = 0.00），并与D8S373显示出提示性连锁（Z = 1.92，θ = 0.00）。一个影响SBP的QTL与D21S1440显示出提示性连锁（Z = 2.82，θ = 0.00）以及与D18S844显示出提示性连锁（Z = 2.09，θ = 0.11）。若模型中没有基因型特异性效应，与D2S1790的连锁甚至不具有提示性（Z = 1.33，θ = 0.09）；因此，基因型特异性建模对于检测这种连锁至关重要。与其他人群的连锁研究比较表明，在魁北克家族研究中，在相同标记处也复制了与D
