Genome-wide linkage analysis of blood pressure in Mexican Americans

The genetic mechanisms that control variation in blood pressure level are l argely unknown. One of the first steps in understanding those mechanisms is the localization of the genes that have a significant effect on blood pres sure. We performed genome scans of systolic (SBP) and diastolic blood press ure (DBP) on a population-based sample of families in the San Antonio Famil y Heart Study. A likelihood-based Mendelian model incorporating genotype-sp ecific 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) link age on 399 polymorphic markers. Results showed that the genotype-specific c ovariate effects were highly significant for both SEP and DBP. Linkage resu lts showed that a quantitative trait locus (QTL) influencing DBP was signif icantly linked to D2S1790 (Z = 3.92, theta = 0.00) and showed suggestive li nkage to D8S373 (Z = 1.92, theta = 0.00). A QTL influencing SEP showed sugg estive 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 link age to D2S1790 was not even suggestive (Z = 1.33, theta = 0.09); thus genot ype-specific modeling was crucial in detecting this linkage. A comparison w ith linkage studies based in other populations showed that the significant linkage to D2S1790 has been replicated at the same marker in the Quebec Fam ily Study. The replicated significant linkage at D2S1790 may begin to estab lish the locations of the genes that significantly affect blood pressure ac ross several human ethnic groups. (C) 2001 Wiley-Liss. Inc.