Heritability of MI/CAD explained by three genomic compartment sets.

<p>Heritability estimates were inferred independently first in MIGen and WTCCC CAD from a single model involving three variance components (“genic coding”, “genic noncoding” and “intergenic”) using the GCTA software [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005622#pgen.1005622.ref022" target="_blank">22</a>,<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005622#pgen.1005622.ref023" target="_blank">23</a>]. Heritability estimates shown here are from a meta-analysis of the Variance and standard error (V-SE) from these models using as weights the inverse variance from these models.</p><p>¹Variance and V-SE are estimates from the ratio of genetic variance to phenotypic variance for the specified variance component whereas the <i>P</i> value (V-P) is from the likelihood ratio test of a reduce model with the specified genetic variance component dropped from the full model, from the restricted maximum likelihood method in the GCTA software [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005622#pgen.1005622.ref022" target="_blank">22</a>,<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005622#pgen.1005622.ref023" target="_blank">23</a>].</p><p>²Enrichment of variance was calculated as the % variance of total divided by % SNPs of total. MI, myocardial infarction; CAD, coronary artery disease; SNP, single nucleotide polymorphism.</p><p>³<i>P</i> value from difference in the observed variance minus the expected variance (variance of whole genome as sum multiplied by % SNPs of total). Genic coding, variants that code amino acid sequence within ±10 kilobases of the 3′ or 5′ untranslated regions of a gene. Genic noncoding, variants that do not code amino acid sequence within ±10 kilobases of the 3′ or 5′ untranslated regions of a gene. Intergenic, variants that are beyond ±10 kilobases of the 3′ or 5′ untranslated regions of a gene.</p><p>We calculated the SNP-heritability in three genomic compartment sets for MI/CAD in a meta-analysis of the MIGen and WTCCC CAD studies using the Genome-wide Complex Trait Analysis (GCTA) software. We observed increased enrichment in variance in both “genic coding” and “genic noncoding” regions.