Genetic control of lipoprotein(a) concentrations is different in Africans and Caucasians

Lipoprotein(a) (Lp(a)) represents a quantitative trait in human plasma asso ciated with atherothrombotic disease. Large variation in the distribution o f Lp(a) concentrations exists across populations which is at present unexpl ained. Sib-pair linkage analysis has suggested that the apo(a) gene on chro mosome 6q27 is the major determinant of Lp(a) levels in Caucasians, We have here dissected the genetic architecture of the Lp(a) trait in Africans (Kh oi San, South African Blacks) and Caucasians (Austrians) by family/sib-pair analysis. Heritability estimates ranged from h(2) = 51% in Blacks, h(2) = 61% in Khoi San, to h(2) = 71% in Caucasians, Analysis by a variance compon ents model also demonstrated that the proportion of the total phenotypic va riance explained by genetic factors is smaller in Africans (65%) than in Ca ucasians (74%). Importantly the sib-pair analysis clearly identified the ap o(a) gene as the major locus in Caucasians which explained the total geneti c variance. In the African samples the apo(a) gene accounted for only half the genetic variance. Together with previous results from population studie s our data indicate that genetic control of Lp(a) levels seems to be distin ctly different between Africans and Caucasians. In the former genetic facto rs distinct from the apo(a) locus and also non-genetic factors may play a m ajor role.