Genetic signals common to 14 psychiatric disorders found in the DNA of more than one million people

The purpose of this research is to better differentiate psychiatric diagnoses by considering their genetic characteristics, because the clinical reality is that the expression of human suffering is complex and diverse, leading to a person receiving several diagnoses simultaneously, or diagnoses changing throughout their follow-up. To this end, they employ various genomic analyses in a sample of over one million people with diagnoses grouped into fourteen categories.

The findings have no impact on clinical practice, but they continue to support the promising idea that psychiatric diagnoses can be anchored to biological variables.

Psychiatric diagnoses, the subject of this type of research, are considered facts of nature, when in fact they are subjective clinical judgments made, moreover, based on the subjectivity of individuals: we lack hard, objective, and unequivocal data to confirm them. Psychiatric diagnoses are social constructs made by consensus, which change in number and definition in successive editions of diagnostic manuals, overlap with each other, and are conditioned by cultural and social factors, so that their genetic correlation is necessarily imprecise, as this study shows.

When considering the onset of a psychiatric disorder, a biopsychosocial model must be taken into account. Genetic studies in recent years have revealed that genetic predisposition to psychiatric disorders is due to thousands of variants distributed throughout the genome, and that many of these variants confer risk for different psychiatric disorders. This article, which analyzes shared genetic susceptibility, will be the reference work in psychiatric genetics in the coming years. Not because of its novelty, but because of the large amount of data analyzed. The article is an update of previous analyses, including a greater number of disorders (mainly addictive disorders) and a greater number of patients analyzed for each disorder. This data has been obtained thanks to the efforts of several hundred researchers from dozens of countries collaborating in the genetic psychiatry consortium. No new data of this magnitude is expected in the coming years.

The article uses different cutting-edge analysis methods that complement each other. The results between the different methods are consistent and convergent, which reinforces the findings.

Rather than presenting major new developments, the article consolidates previous evidence on the structure of psychopathology, with a genetic factor for general psychopathology and others more specific to groups of disorders. The genetic variants specific to a particular psychiatric disorder are minimal. This explains a very common phenomenon in psychiatry, the presence (simultaneous or sequential) of more than one psychiatric disorder in the same person. In addition, the study lays the foundation for a new classification of psychiatric disorders with greater biological validity, taking into account this hierarchical structure of psychopathology. This could have implications for treatment, which could focus on the identified transdiagnostic factors.

The study helps to interpret, at the genetic level, the factor of general psychopathology. There are various hypotheses about what this factor represents. The results of the study suggest that it may be related to a general tendency to have negative emotions (such as anxiety, stress, worry, etc.).

Among the limitations of the study, as is almost always the case in this type of research, the patients are of European descent. Given that genetic factors can interact with psychosocial factors (which can vary between different populations), these findings need to be confirmed in more diverse patient samples in order to generalize them.

Furthermore, increasing the number of samples often comes at the expense of a poorer definition of the diagnosis, which could inflate this shared genetic susceptibility. There is also genetic heterogeneity within the same diagnosis, something that is not taken into account in the studies on which this article is based. For example, it has recently been shown that the genetic bases of early-onset and late-onset depressive disorder are very different.

Despite these limitations, the general aspects of the work are based on a very solid foundation, which will constitute the general framework of psychiatric genetics in the coming years.