Table 1.

Definitions of historical and contemporary molecular genetic techniques

Method	Definition
Family study	Compares the prevalence of a trait of interest in family members of individuals with the trait of interest to family members of those without the trait of interest.
Twin study	Correlations between monozygotic (MZ) and dizygotic (DZ) twins for a trait of interest are compared to determine the extent to which variation in the trait is due to genetic and environmental factors. Because MZ twins are presumed to share 100% and DZ twins 50% of their genetic makeup, if the correlation for a trait is twice as strong in MZ than DZ twins, genetic factors are implicated.
Linkage study	Identifies regions of the genome involved in genetic risk for a trait through samples of multiplex families. Does not identify specific genes involved in risk, only chromosomal regions.
Candidate gene study	Examines the allele frequency of an a priori selected single nucleotide polymorphism (SNP) in individuals with and without a trait of interest.
Genome-wide association study (GWAS)	Compares individuals with and without a trait of interest on 300,000 to 1,000,000 genetic markers across the genome simultaneously. Genome-wide statistical significance is indicated by p < 5×10-8.
Copy number variation (CNV)	Examines the presence of genomic repeats or deletions in individuals with trait of interest.
Linkage disequilibrium score regression (LDSC)	Statistical method used to determine the genetic correlation between traits.
Polygenic risk score (PRS)	Uses GWAS information from all SNPs to create an individual genetic risk profile for association with a trait.
High-throughput sequencing	Uses next-generation DNA sequencing techniques to examine variants associated with disease.
Gene-environment correlation (rGE)	Environmental factors influence genetic risk for a trait.
Gene-by-environment interaction (GxE)	Environmental factors enhance or reduce genetic risk or when genetic risk influences response to an environment.