PLoS Genet 8(3): e1002637. doi:10.1371/journal.pgen.1002637
Shashaank Vattikuti, Juen Guo, and Carson C. Chow
Abstract: We used a bivariate (multivariate) linear mixed-effects model to estimate the narrow-sense heritability (h2) and heritability explained by the common SNPs (hg2) for several metabolic syndrome (MetS) traits and the genetic correlation between pairs of traits for the Atherosclerosis Risk in Communities (ARIC) genome-wide association study (GWAS) population. MetS traits included body-mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure (SBP), fasting glucose (GLU), fasting insulin (INS), fasting trigylcerides (TG), and fasting high-density lipoprotein (HDL). We found the percentage of h2 accounted for by common SNPs to be 58% of h2 for height, 41% for BMI, 46% for WHR, 30% for GLU, 39% for INS, 34% for TG, 25% for HDL, and 80% for SBP. We confirmed prior reports for height and BMI using the ARIC population and independently in the Framingham Heart Study (FHS) population. We demonstrated that the multivariate model supported large genetic correlations between BMI and WHR and between TG and HDL. We also showed that the genetic correlations between the MetS traits are directly proportional to the phenotypic correlations.
Author Summary: The narrow-sense heritability of a trait such as body-mass index is a measure of the variability of the trait between people that is accounted for by their additive genetic differences. Knowledge of these genetic differences provides insight into biological mechanisms and hence treatments for diseases. Genome-wide association studies (GWAS) survey a large set of genetic markers common to the population. They have identified several single markers that are associated with traits and diseases. However, these markers do not seem to account for all of the known narrow-sense heritability. Here we used a recently developed model to quantify the genetic information contained in GWAS for single traits and shared between traits. We specifically investigated metabolic syndrome traits that are associated with type 2 diabetes and heart disease, and we found that for the majority of these traits much of the previously unaccounted for heritability is contained within common markers surveyed in GWAS. We also computed the genetic correlation between traits, which is a measure of the genetic components shared by traits. We found that the genetic correlation between these traits could be predicted from their phenotypic correlation.
I am very happy that this paper is finally out. It has been a three year long ordeal. I’ll write about the story and background for this paper later.