Table 4.
Potential biomarkers from genomics/NGS studies in various MH-related disorders
| Author name or study ID | Disorder | Genes/biological functions affected | Implications/key findings | Source |
|---|---|---|---|---|
| Bertram et al.’s [38] | AD | APP, TREM2 and PLD3 | Gene mutations associated with AD | Various |
| Iacono et al. [142] | AD | A study of mouse models in AD using single-cell RNA sequencing (scRNA-seq) and functional analysis identified genes associated with gene expression or metabolic processes | Genes linked with multiple mouse organs were found to be associated | Brain |
| Verheijen [39] | EOAD | Increased accumulation of the amyloid-β (Aβ)1–42 peptide. Genes associated included amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) | Hundreds of pathogenic mutations were found in this inherited disorder | brain |
| Verheijen [39] | LOAD | APOE ε4 allele | Well-known risk factor | Brain |
| Pantazatos et al. [143] | MDD | Humanin-like-8 (MTRNRL8), interleukin-8 (IL8) and serpin peptidase inhibitor, clade H (SERPINH1) and chemokine ligand 4 (CCL4) | Altered gene expression identified using RNA-seq | Brain |
| Nashed et al. [41] | MDD | Neuronal development, intracellular signaling, learning and memory | Pathways implicated in depression using RNA-seq | Brain |
| Pantazatos et al. [144] | MDD | SSAT and SATX isoforms, SAT1 | Low gene expressions in MDD | Brain |
| Pirooznia et al. [145] | MDD | Calcium signaling and dendrite regulation | Exons of synaptic genes potentially involved in the etiology of MDD | Brain |
| Howard et al. [146] | MDD | 102 genomic variants and 269 genes including SORCS3 and NEGR1 | Meta-analysis study of three large genome-wide association studies (GAWAS) studies | Brain |
| Keller et al. [42] | MDD | Variants in the NR3C1 gene including rs33388, rs10052957, rs10482633, rs41423247. variants in the NR3C2 gene included rs1879829, rs3910052, rs4835488, rs6535578, rs7658048 and rs5522 | NR3C2, NR3C1 variants affecting HPA axis and cognition | Brain |
| Belzeaux et al. [147] | MDD | RORA, GCET2 and SMARCC2 | Three potential biomarkers for treatment response | Various |
| Feng et al. [148] | MDD | EEF2, RPL26L1, RPLP0, PRPF8, LSM3, DHX9, RSRC1 and AP2B1 | potential pathogenic genes associated with MDD and potential therapeutic targets | Various |
| Multiple studies [17, 43] | MDD | SNPs of CRHR1 | Candidate genes reported | various; blood |
| Multiple studies [149–151] | MDD | Whole-genome sequencing was used to identify SNPs: one near gene SIRT1, an enzyme that deacetylates proteins that contribute to cellular regulation and the other SNP in an intron of LHPP gene [149–151] | Single nucleotide polymorphisms (SNPs) associated with MDD | Various; blood; saliva |
| Multiple studies [35, 152, 153] | SCZ and BD | Mutations and DNA methylation in BRD1 protein | Genetic associations | Various; blood; blood |
| Pies et al. [7, 44] | SCZ | Mutations in neuregulin-1 NRGI | Potential biomarkers for SCZ; increased risk of SCZ | Various; various |
| Multiple studies [35, 154, 155] | SCZ | ZNF804A [35, 155] and CRMP2 mutations [35, 154] | Increased risk of SCZ | Various; blood; mouse models, cell lines and DNA constructs |
| [49] | SCZ | Voltage-gated calcium channels, ARC-associated scaffold and FMRP interactors | The affected functional gene sets were identified using whole exome sequencing (WES) | Induced pluripotent stem cells (iPSC) |
| Demkow et al. [133] | ASD, ADHD | NGS testing justification in various clinical scenarios | Enables search for inherited conditions and new de novo mutations | Various |
| Goes et al. [156] | ASD | RPGRIP1L, FRAS1, AHNAK, KDM5B and SLC12A4 | Shortlisted genes implicated in ASD using WES | DNA from lymphoblastoid cell lines |
| Multiple studies [51, 52] | ADHD | Mutations in dopamine transporter and D4 receptor | Potential biomarkers | Various |
| Li et al. [48] | ASD, epileptic encephalopathy (EE), intellectual disability (ID), SCZ | 53 shared genes among four disorders, including SCN2A | Indicates a shared etiology of these disorders | Various |
| [49] | SCZ and ASD | Synaptogenesis and synapse function and epigenetic process | Common pathways found | Induced pluripotent stem cells (iPSC) |
| Wen et al. [157] | ASD | Mutations in MECP2 | Used WES to identify several loss-of-function mutations that could lead to ASD | Peripheral blood |
| Multiple studies: Sjaarda et al. [17, 50] | ASD and PTSD | Serotonin transporter SLC6A4 | Mutations linked to ASD and prenatal stress; GWAS-identified polymorphisms associated with PTSD | Mouse model; various |
| [17] | PTSD, generalized anxiety disorder (GAD) and Parkinson (PD) | RGS2 | Only a few findings have been confirmed by multiple studies | Various |