What psychiatric genetics can and cannot tell an Indian family

When a young man first came to the clinic with symptoms of psychosis, his parents were eager to know when he would be able to return to college. Although this is a common initial concern, later discussions often shifted to more profound questions. Parents frequently wondered if the illness had a genetic component and whether their child would undergo genetic testing.

Their thoughts centered on whether they had inadvertently caused the illness, if their child's future was predetermined, and if the diagnosis would impact their family life, including marriage prospects and the ability to have healthy children. Generally, families do not inquire about psychiatric genetics due to scientific intrigue; instead, they seek explanations and a sense of relief from blame.

Colloquial expressions like "genes for schizophrenia" or "genes for depression" can be misleading. While genetic research has advanced significantly, it is crucial to understand that genes alone do not dictate a person's fate. What is more important is that vulnerability is complex and intertwined with the individual's life experiences.

A key tool in this field is the genome-wide association study (GWAS), which analyzes millions of genetic variants across large groups of people with and without a specific condition. In common psychiatric disorders, no single gene variant has as significant an impact as in monogenic diseases such as Tay-Sachs or Duchenne muscular dystrophy.

In other words, risk is polygenic, arising from the combined influence of thousands of variants, rare genetic changes, development, environment, and chance. A landmark schizophrenia study in 2022 identified associations at 287 genomic regions, revealing genes active in neurons and synapses. A comparable bipolar disorder study in 2021 identified 64 associated regions.

However, it is essential to note that a genomic region is not equivalent to a gene, and an association does not necessarily imply causation. Many 'signals' may be related to stretches of DNA that regulate gene expression rather than directly encoding proteins. Several genes might be located near the same signal, and the relevant effect could occur during a specific period of brain development.

While GWAS studies have illuminated potential biological mechanisms and treatment options, they also reveal a disconnect between traditional diagnostic criteria and biological realities. For example, a 2025 study published in Nature found that inherited risk is shared across schizophrenia and bipolar disorder, suggesting that mental illness is not organized neatly according to the DSM manual's categories.

Despite this, diagnostic labels remain valuable for guiding treatment and communicating prognosis to patients and their families. Nevertheless, polygenic risk scores, which attempt to estimate an individual's inherited susceptibility to mental illness, have limitations. These scores cannot predict whether someone will develop the illness, at what age, how severe it will be, or which medication will be most effective.

A person with a higher risk score may remain healthy, while someone with a lower score may still develop the condition, as risk scores only capture a portion of the genetic liability and do not account for other factors like childhood adversity, sleep disturbances, substance use, medical illnesses, social support, and access to timely care.

It is also important to consider that genomic databases have historically underrepresented individuals of non-European ancestry, leading to less accurate scores for diverse populations. The GenomeIndia project, which collected whole-genome data from 10,000 healthy, unrelated Indians across 83 population groups, demonstrated the immense genetic diversity within India.

Therefore, Indian psychiatrists must exercise caution when using polygenic risk scores, as they may not accurately reflect the population's genetic makeup. Ultimately, psychiatric genetics can be beneficial in consultations by helping to alleviate blame. A mother should not be blamed for causing schizophrenia, nor should a father be held responsible for transmitting bipolar disorder through a moral failing.

Genetics provides valuable insights, but it should not lead to fatalism. While biological factors play a role, mental illness is also influenced by a multitude of environmental and social factors. In the consultation room, genetics can help reduce blame and foster a more nuanced understanding of mental health.