The genetic dissection of complex traits in a founder population.
We estimated broad heritabilities (H(2)) and narrow heritabilities (h(2)) and conducted genomewide screens, using a novel association-based mapping approach for 20 quantitative trait loci (QTLs) among the Hutterites, a founder population that practices a communal lifestyle. Heritability estimates ranged from.21 for diastolic blood pressure (DBP) to.99 for whole-blood serotonin levels. Using a multipoint method to detect association under a recessive model we found evidence of major QTLs for six traits: low-density lipoprotein (LDL), triglycerides, lipoprotein (a) (Lp[a]), systolic blood pressure (SBP), serum cortisol, and whole-blood serotonin. Second major QTLs for Lp(a) and for cortisol were identified using a single-point method to detect association under a general two-allele model. The heritabilities for these 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 measures of heritability and the strength of association on a genomewide screen (P>.50), suggesting that heritability estimates per se do not identify phenotypes that are influenced by genes with major effects. The present study demonstrates the feasibility of genomewide association studies for QTL mapping. However, even in this young founder population that has extensive linkage disequilibrium, map densities <<5 cM may be required to detect all major QTLs.
Ober
C
C
Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. c-ober@genetics.uchicago.edu
Abney
M
M
McPeek
M S
MS
D000293:Adolescent; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D002648:Child; D002874:Chromosome Mapping / Q000379:methods*; D003404:Creatinine / Q000652:urine; D017097:Electric Impedance; D004804:Eosinophils / Q000166:cytology; D005260:Female; D018703:Founder Effect; D005819:Genetic Markers / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007073:Immunoglobulin E / Q000097:blood; D007328:Insulin / Q000097:blood; D007610:Kallikreins / Q000652:urine; D007958:Leukocyte Count; D008168:Lung / Q000502:physiology; D008297:Male; D008957:Models, Genetic; D020412:Multifactorial Inheritance / Q000235:genetics*; D010375:Pedigree; D019655:Quantitative Trait, Heritable; D012701:Serotonin / Q000097:blood; D013023:South Dakota
D005819:Genetic Markers; D007328:Insulin; D012701:Serotonin; D007073:Immunoglobulin E; D003404:Creatinine; D007610:Kallikreins; D006854:Hydrocortisone