Common SNPs explain a large proportion of the heritability for human height

When causal SNPs are selected at random, this is the GCTA model that has been used in genetic studies of complex traits.

“We note that when the causal SNPs are selected at random, this is the GCTA model that has been used in genetic studies of complex traits (Yang et al., 2010).”

One third (9 out of 31) of the identified MHC variants lie within either intergenic regions or a long-range haplotype that contains several non-classical HLA and other non-HLA genes.

“One third (9 out of 31) of the identified variants lie within either intergenic regions or in a long-range haplotype that contains several non-classical HLA and other non-HLA genes.(17)”

Sensitivity analysis showed negligible differences in heritability estimates between BOLT-LMM and restricted maximum likelihood analysis implemented using BOLT-REML.

“after sensitivity analysis showed negligible differences in estimates between BOLT-LMM and restricted maximum likelihood analysis67 implemented using the BOLT-REML software tool.”

GWAS power is limited, but statistical methods can estimate SNP-heritability and characterize genetic architecture even when few associations are significant.

“Even when genome-wide significant associations are few, statistical methods can be used to estimate “SNP-heritability,” a measure of the total genetic effect5, and to characterize nearly every aspect of genetic architecture.”

Direct empirical support for the infinitesimal model comes from genomic variance analyses.

“Direct empirical support for the infinitesimal model comes from genomic variance analyses70, 71.”

Regression of phenotypic similarity on genetic relatedness implies that common variants capture the majority of genetic variants.

“A multivariate version of this approach, implemented by regression of phenotypic similarity on genetic relatedness, also implies that common variants capture the majority of the genetic variants71.”

Mixed linear modeling attributes over half of height phenotypic variation to common variants.

“over 50% of the phenotype can be attributed to common variants using the mixed linear modeling approach71”

Height has a heritability as high as 80%.

“However, in the case of height, where heritability is as high as 80%, over 50% of the phenotype can be attributed to common variants using the mixed linear modeling approach71”

Once allele-frequency skews and incomplete LD are corrected, nearly all of height's genetic contribution is assigned to genotypic variation.

“and after adjustment for allele frequency skews and incomplete LD, essentially the entire genetic contribution has been ascribed to genotypic variation.”

The correlation of normalized and centered genotype counts is well suited as a measure of genetic relatedness when considering differences across genetically diverse populations.

“This relatedness measure is widely used to control for population structure in cohorts drawn from multiple mating populations (e.g., genetic principal components analysis or as the covariance structure of random effects in linear-mixed models of genetic association tests) and, thus, is well suited as a measure of genetic relatedness when considering differences across genetically diverse”

The heritability for height in Europeans (hg2 = 0.394; N = 1,825) is similar to previously reported estimates.

“The heritability for height in Europeans (hg2 = 0.394; N = 1,825) is similar to previously reported estimates [18].”

The top four genetic PCs were included as covariates in the model to correct for population structure, which can inflate heritability estimates.

“The top four genetic PCs were included as covariates in the model to correct for population structure, which can inflate heritability estimates [18,69,70].”