Table 1 Evolution of genomic markers for disease mapping/discovery of risk loci for complex disorders, including schizophrenia.
From: Rediscovering tandem repeat variation in schizophrenia: challenges and opportunities
1980s/1990s | 2000s | 2010s | 2020s?? | |
|---|---|---|---|---|
Genomic marker | -RFLPs (restriction fragment length polymorphisms) -“Microsatellites” (short tandem repeats) | SNPs (single-nucleotide polymorphism) | SNVs (single-nucleotide/protein-coding variants) | ?Re-discovering -“Microsatellites” (short tandem repeats) and -“Macrosatellites” (variable number tandem repeats) -Other structural variants |
Population genomics reference | Genetic linkage maps ~400 markers (1987) ~5000 microsatellite markers (1996) | Catalogued SNPs/linkage disequilibrium 1 million SNPs (2005, HapMap) 3 million SNPs (2007, HapMap) | SNVs catalogued in reference genome ~10,000 SNVs (2008) | Tandem repeats catalogued in reference genome ~1 million tandem repeats (tandem repeat finder, 2022) |
Study design | Linkage analyses/candidate gene approach of genotyped cohorts | Genome-wide association studies of genotyped cohorts | Genome-wide profiling of whole-exome-sequenced cohorts | Genome-wide profiling of whole-genome-sequenced cohorts |
Schizophrenia (SCZ) application/example | Numerous reports, inconsistent findings and overall lack of replication | Psychiatric Genomics Consortium, 2014: 36,989 SCZ cases; 113,075 CONT 108 significant independent loci 2022: 76,755 SCZ cases, 243,649 CONT 287 significant independent loci | Schizophrenia Exome Sequencing Consortium 2022: 24,248 SCZ cases, 97,322 CONT 10 significant genes with coding variants |
