Fine-mapping

Fine-mapping is a set of methods in genetics used to identify the genetic variant or variants, often single-nucleotide polymorphisms (SNPs), most likely to explain an observed association between a genetic locus and a phenotype. It is commonly used during genetic association studies, including quantitative trait locus (QTL) analyses and genome-wide association studies (GWAS). In QTL analysis, regions of the genome are tested for association with variation in a quantitative trait. Many QTL studies measure molecular traits, such as gene expression, chromatin accessibility, splicing or protein abundance, and are therefore often described as molecular QTL studies. One example is an expression quantitative trait locus (eQTL), in which genetic variants at a locus are associated with differences in gene expression. This could for instance occur if the variant falls in the promoter of the gene, thereby affecting binding of a transcription factor which regulates gene expression. On the other hand, in GWAS, genetic variants across the genome are tested for association with traits or diseases, often organism-level phenotypes. In both QTL studies and GWAS, an association signal often does not identify a single causal variant in a locus. This is due to a phenomenon called genetic linkage, where alleles close together on a chromosome are often inherited together during meiosis.…

Fine-mapping is a set of methods in genetics used to identify the genetic variant or variants, often single-nucleotide polymorphisms (SNPs), most likely to explain an observed association between a genetic locus and a phenotype. It is commonly used during genetic association studies, including quantitative trait locus (QTL) analyses and genome-wide association studies (GWAS). In QTL analysis, regions of the genome are tested for association with variation in a quantitative trait. Many QTL studies measure molecular traits, such as gene expression, chromatin accessibility, splicing or protein abundance, and are therefore often described as molecular QTL studies. One example is an expression quantitative trait locus (eQTL), in which genetic variants at a locus are associated with differences in gene expression. This could for instance occur if the variant falls in the promoter of the gene, thereby affecting binding of a transcription factor which regulates gene expression. On the other hand, in GWAS, genetic variants across the genome are tested for association with traits or diseases, often organism-level phenotypes. In both QTL studies and GWAS, an association signal often does not identify a single causal variant in a locus. This is due to a phenomenon called genetic linkage, where alleles close together on a chromosome are often inherited together during meiosis. Genetic linkage can contribute to linkage disequilibrium (LD), the non-random association of alleles at different loci in a population. Therefore, several nearby variants are inherited together more often than expected by chance. Suppose that two nearby SNPs are usually inherited together, so that allele T at one SNP is commonly found on the same chromosome as allele G at another SNP. If the T allele affects a phenotype, association testing may also detect an association with G, even if G has no biological effect. Fine-mapping attempts to distinguish the variant that is more likely to cause the trait from nearby variants that are only associated because of LD.

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