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Genome-wide complex trait analysis
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<p>Genome-wide complex trait analysis (GCTA) Genome-based <a href="/facts/Restricted_maximum_likelihood/9tybgT1E">restricted maximum likelihood</a> (GREML) is a statistical method for <a href="/facts/Heritability/REQ3CfRe">heritability</a> estimation in genetics, which quantifies the total additive contribution of a set of genetic variants to a trait. GCTA is typically applied to common single nucleotide polymorphisms (<a href="/facts/SNPs/Qy5Y2wom">SNPs</a>) on a genotyping array (or "chip") and thus termed "chip" or "SNP" heritability. </p><p>GCTA operates by directly quantifying the chance genetic similarity of unrelated individuals and comparing it to their measured similarity on a trait; if two unrelated individuals are relatively similar genetically and also have similar trait measurements, then the measured genetics are likely to causally influence that trait, and the correlation can to some degree tell how much. This can be illustrated by plotting the squared pairwise trait differences between individuals against their estimated degree of relatedness. GCTA makes a number of modeling assumptions and whether/when these assumptions are satisfied continues to be debated. </p><p>The GCTA framework has also been extended in a number of ways: quantifying the contribution from multiple SNP categories (i.e. functional partitioning); quantifying the contribution of Gene-Environment interactions; quantifying the contribution of non-additive/non-linear effects of SNPs; and bivariate analyses of multiple phenotypes to quantify their genetic covariance (co-heritability or <a href="/facts/Genetic_correlation/qzKazGr6">genetic correlation</a>). </p><p>GCTA estimates have implications for the potential for discovery from <a href="/facts/Genome-wide_association_study/qemSYa3a">Genome-wide Association Studies (GWAS)</a> as well as the design and accuracy of <a href="/facts/Polygenic_scores/TLq1Cdly">polygenic scores</a>. GCTA estimates from common variants are typically substantially lower than other estimates of total or narrow-sense heritability (such as from twin or kinship studies), which has contributed to the debate over the <a href="/facts/Missing_heritability_problem/ex1ugFU7">Missing heritability problem</a>. </p>