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Nat Genet ; 46(12): 1356-62, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25383972

ABSTRACT

Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)γ). We show that h(2)γ = 2FSTCθ(1 - θ)h(2), where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h(2) estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h(2)g in these and other data but smaller than family-based estimates of h(2).


Subject(s)
Genetics, Population/methods , Genome-Wide Association Study , Multifactorial Inheritance , Quantitative Trait, Heritable , Black or African American/genetics , Aged , Black People , Body Mass Index , Cardiovascular Diseases/genetics , Case-Control Studies , Chromosome Mapping , Cohort Studies , Computer Simulation , Epistasis, Genetic , Female , Genotype , Humans , Male , Middle Aged , Models, Genetic , Models, Statistical , Phenotype , Polymorphism, Single Nucleotide , Prostatic Neoplasms/genetics , Reproducibility of Results , United States
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