The genetic dissection of complex traits in a founder population

We estimated broad heritabilities (H-2) and narrow heritabilities (h(2)) an d conducted genomewide screens, using a novel association-based mapping app roach for 20 quantitative trait loci (QTLs) among the Hutterites, a founder population that practices a communal lifestyle. Heritability estimates ran ged from .21 for diastolic blood pressure (DBP) to .99 for whole-blood sero tonin levels. Using a multipoint method to detect association under a reces sive model we found evidence of major QTLs for six traits: low-density lipo protein (LDL), triglycerides, lipoprotein (a) (Lp[ a]), systolic blood pres sure (SBP), serum cortisol, and whole-blood serotonin. Second major QTLs fo r Lp( a) and for cortisol were identified using a single-point method to de tect association under a general two-allele model. The heritabilities for t hese six traits ranged from .37 for triglycerides to .99 for serotonin, and three traits (LDL, SBP, and serotonin) had significant dominance variances (i.e., H-2/h(2)). Surprisingly, there was little correlation between measu res of heritability and the strength of association on a genomewide screen (P>.50), suggesting that heritability estimates per se do not identify phen otypes that are influenced by genes with major effects. The present study d emonstrates the feasibility of genomewide association studies for QTL mappi ng. However, even in this young founder population that has extensive linka ge disequilibrium, map densities much less than 5 cM may be required to det ect all major QTLs.