Glossary of terms

Association mappinga trait mapping approach that analyzes the co-occurrence of the trait and the marker in multiple individuals of a population; it relies on historical recombination.
Copy number variantA segment of DNA that is present at variable copy number among individuals when compared to a diploid reference genome. Several publicly available catalogs of CNVs in the human genome are available (e.g.,;
EpistasisThe phenomenon where the effect of a gene (or variant) on a trait is not independent of the effect on the trait of another gene (or variant).
Expression QTL (eQTL)a region of the genome harboring a genetic variant contributing to gene expression variation. These are identified through association mapping (eQTL mapping) of variable transcription levels among individuals.
Fine mappinga methodology to resolve locus boundaries. However the same LD that facilitates GWAS hampers fine mapping. In addition, multi-SNP analyses can help to refine the signal. Haplotype analyses using SNPs showing statistically independent association signals could reveal the existence of a single associated haplotype, refining the LD criterion for considering variants as putatively functional or could suggest multiple causal variants. Mapping in populations of different ancestry (that have different LD structure) may also help to refine a locus of interest.
Functional genomicsa field of study that combines genetics and molecular biology to understand the function of genes and other features of the genome.
Gene set enrichment analysisA computational method that determines whether an a priori defined set of genes shows statistically significant, concordant differences between two states (e.g., different phenotypes or associated vs. nonassociated genetic variants).
Genetic architecture(1) the number of loci affecting a complex trait, (2) the distribution of their effects, and (3) their interactions with each other (including dominance and epistatic effects) and with environmental variation. Although classically genetic architecture can be viewed as the decomposition of genetic variance for a trait into additive and interaction components, and (1) and (2) above are subsumed within additive genetic variance, in the GWAS era, we can directly investigate the number of loci and their distribution of effects.
Genetic heterogeneitythe phenomenon wherein different genetic variants underlie a single phenotypic trait in different individuals/families.
Imputationa method to estimate genotypes of an individual at unmeasured SNP loci using a known reference panel of genetic variation and haplotypes derived from a sample of close ancestry.
Linkage mappinga trait mapping approach that analyzes cosegregation of a trait with a marker in family pedigrees.
Mendelian diseasea disease in which mutations in a single gene cause the phenotype and for which the pattern of inheritance is very clear.
Meta-analysisa term describing a wide variety of statistical procedures developed to pool and summarize results from multiple studies, thereby increasing statistical power.
Odds ratio (OR)a statistic used to assess the likelihood of a particular outcome (e.g, disease state) if a certain factor (or allelic variant) is present. In the context of disease mapping, whether the odds ratio is greater than or less than one indicates whether a variant is a risk variant or protective, and the magnitude of the OR can be interpreted as the effect size. An OR of 1 indicates that the condition or event under study is equally likely in both groups.
Penetrancethe extent to which a genetic variant has an effect on individuals who carry it. High penetrance would refer to a Mendelian disease.
Pleiotropythe phenomenon wherein a single gene or variant affects multiple phenotypes.
Prospective cohorta set of individuals that is followed over time with repeated observational measurements taken throughout. The key feature is that traits studied at a subsequent point in time are being examined in a set of individuals that was not selected on the basis of that trait.
Systems geneticsholistic study of the effects of one or more genetic variants on the outcome (complex trait phenotype) and/or intermediate phenotypes such as gene expression profiles or other functional genomic or cell biological data.
The International HapMap Projectan international consortium to create a catalog of common genetic variation, primarily SNPs that occur in humans. The data reveal where genetic variants occur in the genome, how correlated they are with one another (linkage disequilibrium), and how they are distributed among individuals within and among populations. All data are publicly available;
The 1000 Genomes Projectan international consortium-led project to fully sequence the genomes of at least 1000 people (now approximately 2000 people) of multiple ancestries from around the world. The project identifies SNPs as well as structural variants (rearrangements, deletions, or duplications of segments of the human genome). All data are publicly released as they become available;