Genetic approaches for the identification of genes implicated in psychiatric diseases

Human molecular Genetics
Centro de Biología Molecular “Severo Ochoa” CSIC-UAM (CBMSO)

Family studies have established a strong genetic contribution for most psychiatric diseases, but the specific genes involved still remain largely unknown.

We adopt several genomic approaches to identify susceptibility genes implicated in autism spectrum disorder (ASD), bipolar disorder (BD), and schizophrenia (SCZ). Our analyses are based on: i) Genome-wide association studies (GWAS) able to identify Single Nucleotide Variants (SNPs) (common DNA variation) associated with the disorder; ii) Copy number variant (CNV) analysis: small deletions/duplications of genetic material (>50bp) that may represent etiologic causes for diseases; iii) Next Generation Sequencing (NGS): whole exome sequencing (WES) and whole genome sequencing (WGS) are able to identify rare single nucleotide variants (SNVs) and de novo (DN) (rare DNA variation) that may impair the normal function of proteins, and increase the risk of disease.

Projects available include analyses of large datasets (Ref. 1): summary statistics of the Psychiatric Genomics Consortium GWAS, rare coding variants from sequencing consortia or in-house datasets, de novo variants data (cases, controls and unaffected siblings), expression quantitative trait loci (eQTL), databases, etc.

Our expertise in high-throughput data analyses identified several genes in psychiatric disorders: i) We found the 14-3-3 gene family implicated in autism and schizophrenia (Ref.2-3); ii) We identified IRS4 gene disrupted in bipolar disorder (Ref. 4); iv) We showed the involvement of LRP1 gene in schizophrenia via common variants and autism via rare variants (Ref. 5); v) we revealed that higher burden of truncating variants (alleles that disrupt proteins) are associated with severe symptomatology in autism (Ref. 6).


  1. Toma C, et al. (2018) Comprehensive cross-disorder analyses of CNTNAP2 suggest it is unlikely to be a primary risk gene for psychiatric disorders PLoS genetics 14 (12), e1007535
  2. Toma C, et al. (2014) Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations. Mol Psychiatry. 19: 784-90.
  3. Torrico B, ..., Toma C*  and Cormand B*.  (2020) Involvement of the 14-3-3 gene family in autism spectrum disorder and schizophrenia: genetics, transcriptomics, and functional analyses. Journal of Clinical Medicine.
  4. Toma C, et al (2018) An Examination of Multiple Classes of Rare Variants in Extended Families with Bipolar Disorder. Translational Psychiatry. 13;8(1)65.
  5. Torrico B,…, Toma C.  (2019) Truncating Variant Burden in High Functioning Autism and Pleiotropic Effects of LRP1 Across Psychiatric Phenotypes. Journal of Psychiatry and Neuroscience 16; 44:1-10.
  6. Toma C (2020) Genetic variation across phenotypic severity of autism. Trends in Genetics 36:228-231.
Biomolecules & Cell D.
Molecular Biomedicine
Claudio Toma