Psychiatric disorders share a great genetic subsceptibility, while non-psychiatric neurological disorders –such as Alzheimer’s and Parkinson’s- have a more specific genetic, according to an article the journal Science has published. Participants in this new study –the most ambitious and extense on shared genetic factors in brain disorders- are the lecturers Bru Cormand and Raquel Rabionet, from the Faculty of Biology, the Institute of Biomedicine of the UB (IBUB) and the Rare Diseases Networking Biomedical Centre (CIBERER) and the Research Institute Sant Joan de Déu (IRSJD), among more than 500 experts from around the world.
Millions of genetic variants in more than 800,000 people
The new study gathers data on millions of common genetic variants in more than 800,000 people ─among patients and healthy volunteers─ which could be risk factors in 25 neurological and psychiatric disorders (schizophrenia, autism, bipolar disorder, major depression, ADHD, migraine, Alzheimer’s, etc.).
This study is opening new frontiers in research on pathologies affecting the brain, and goes further from describing risk factors of genetic interest in the field of psychiatry. For the first time, research shapes the genetic basis psychiatric and non-psychiatric neurological disorders have in common (such as Alzheimer’s, Parkinson’s, migraine, etc.) and it broadens the interest focus on personality traits which are not regarded as clinical disorders (emotional instability, etc.) and cognitive parameters (school performance, for instance).
Experts focused the analysis on genetic variants that are common among the general population –present in more than 1 % of the individuals- but which can lead to psychiatric or neurological disorders in some combinations. The studied variants are those affecting changes in an only DNA nucleotide (SNPs), which are more abundant in the human genome.
According to the researcher Bru Cormand, head of the UB Research Group on Neurogenetics and member of IBUB, CIBERER and IRSJD, “this study enables us determining the weight common genetic variants in the etiology of brain diseases: that is, describing the genetic architecture of these diseases and separating the shared genetic basis of each disorder’s specificity”.
Psychiatric disorders: a strong genetic basis in common
The study proves there is a strong genetic correlation between schizophrenia, autism, bipolar disorder, major depression and attention deficit/hyperactivity disorder (ADHD). However, it also reveals there is not an important overlapping between genetic risk factors in psychiatric disorders and the other neurological pathologies.
“Some neurological disorders –says Bru Cormand- such as epilepsy, ictus, multiple sclerosis, Parkinson’s and Alzheimer’s, have genetic bases which are different from each other and other psychiatric disorders. The only exception is migraine, a neurological disorder which shares genetics with several psychiatric disorders (such as ADHD, major depression or Tourette syndrome)”.
Testing personality traits and genes
Another of the most innovative elements is the set genetic correlation between some personality traits –such as neuroticism, i.e. emotional instability- with most psychiatric disorders and migraine. Also, they also studied different cognitive measures during childhood, “for instance, the years of received education or how students do at school, which are positively related to psychiatric disorders such as bipolar disorder or anorexia, and negatively related to neurological disorders such as Alzheimer’s disease or ictus”, states researcher Raquel Rabionet (IBUB-IRSJD-CIBERER).
Framed within this study, genotypes were generated through platforms of genetic analysis at a large scale ─genome-wide association studies (GWAS)─ that are available in Spain and many involved countries. “Preliminary data are milions of genotypes from hundreds of thousands of people” adds Bru Cormand. “In such integrating studies, the main difficulty lies in the harmonization of data, in creating a homogeneous set of data to provide later analyses. Therefore it is necessary to apply rigorous quality controls”.
Psychiatric and neurological disorders: a fragile frontier
For many years, the classification of psychological pathologies has not been based on real causes of each disease due the lack of knowledge on the etiology of these disorders. Knowing the specific genes that are involved in a pathology is an advance to improve the classification (nosology), the diagnosis and therapeutic strategies for the disease.
Studies on twins and family members have enabled determining psychiatric disorders have an important genetic base, which is usually over 50 %. Now, thanks to genetic big data, researchers can identify the specific genes that are involved in these pathologies –the genetic landscape- and treat the quantification of genetic risk out of molecular data. Also, applied technology enables making comparisons between disorders, as it occurs in the study published in Science.
Finding genetic coincidences between different psychiatric disorders points out that, probably, current clinical frontiers do not reflect the differenced physiopathologic processes, at least at a genetic level. “This can have an impact regarding the treatment but it is too soon to know how this can affect the election of therapies. However, if we can use new data to classify disorders into new areas based on the subjacent biology, it can help us design more specific and right therapies”, note Cormand and Rabionet.
“At the moment –they conclude- it might be more precise to adapt the current diagnostic classifications in the field of psychiatry. This would not be necessary in neurological disorders; in that case, frontiers are clear both between different areas and for psychiatric disorders”.
The study is also signed by experts of the Research Institute Vall d’Hebron (VHIR-UAB), the Genomic Regulation Centre (CRG), the University Hospital MútuaTerrassa, Hospital de la Santa Creu i Sant Pau, Catalan Health Institute (ICS), Catalan Institute for Applied Neurosciences and Universitat Internacional de Catalunya (UIC Barcelona), among other Spanish institutions. This multicentre study is driven by Brainstorm Consortium, with the leading experts Verneri Anttila, Aiden Corvi and Ben Neale. This international consortium gathers prestigious institutions related to the neurological and psychiatric disorder research, such as PGC (Psychiatric Genomics Consortium), ISGC (International Stroke Genetics Consortium) and IHGC (International Headache Genetics Consortium).
Universitat de Barcelona