Using Extended Genealogy to Estimate Components of Heritability for 23 Quantitative and Dichotomous Traits
0301 basic medicine
Heredity
Genotype
Epidemiology
Quantitative Trait Loci
Iceland
QH426-470
Polymorphism, Single Nucleotide
03 medical and health sciences
616
Genome-Wide Association Studies
Genetics
Humans
Statistical Methods
Biology
Population Biology
Models, Genetic
Siblings
Statistics
Genetic Variation
Human Genetics
Phenotype
Haplotypes
Genetic Epidemiology
Genetic Polymorphism
Population Genetics
Mathematics
Research Article
Genealogy and Heraldry
DOI:
10.1371/journal.pgen.1003520
Publication Date:
2013-05-30T17:02:16Z
AUTHORS (7)
ABSTRACT
Important knowledge about the determinants of complex human phenotypes can be obtained from the estimation of heritability, the fraction of phenotypic variation in a population that is determined by genetic factors. Here, we make use of extensive phenotype data in Iceland, long-range phased genotypes, and a population-wide genealogical database to examine the heritability of 11 quantitative and 12 dichotomous phenotypes in a sample of 38,167 individuals. Most previous estimates of heritability are derived from family-based approaches such as twin studies, which may be biased upwards by epistatic interactions or shared environment. Our estimates of heritability, based on both closely and distantly related pairs of individuals, are significantly lower than those from previous studies. We examine phenotypic correlations across a range of relationships, from siblings to first cousins, and find that the excess phenotypic correlation in these related individuals is predominantly due to shared environment as opposed to dominance or epistasis. We also develop a new method to jointly estimate narrow-sense heritability and the heritability explained by genotyped SNPs. Unlike existing methods, this approach permits the use of information from both closely and distantly related pairs of individuals, thereby reducing the variance of estimates of heritability explained by genotyped SNPs while preventing upward bias. Our results show that common SNPs explain a larger proportion of the heritability than previously thought, with SNPs present on Illumina 300K genotyping arrays explaining more than half of the heritability for the 23 phenotypes examined in this study. Much of the remaining heritability is likely to be due to rare alleles that are not captured by standard genotyping arrays.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (46)
CITATIONS (345)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....