A new study conducted in rural South India has found that people whose parents are blood relatives (consanguineous marriage) have an increased risk of developing schizophrenia compared to the general population.
Key Facts:
- Researchers recruited 120 patients with schizophrenia and 222 healthy controls from the same rural region in South India.
- 10.7% of patients with schizophrenia had parents who were blood relatives, compared to 7.25% of controls. This difference was not statistically significant.
- However, using DNA analysis to estimate inbreeding coefficients, researchers found significantly higher levels of parental consanguinity in schizophrenia patients versus controls.
- 62.5% of patients had an inbreeding coefficient indicating parental consanguinity, compared to 48.6% of controls.
- The study provides evidence that parental consanguinity increases schizophrenia risk, suggesting multiple recessive genetic factors contribute to the disorder.
Source: Asian Journal of Psychiatry 2021
Link Between Consanguinity & Disease Risk
Consanguineous marriage, where couples are blood relatives, is common in many parts of the world including the Middle East, North Africa and South Asia.
These marriages between close biological kin increase the risk of certain genetic disorders in offspring.
When two copies of a rare recessive mutation are inherited from parents who both carry it, the child is predisposed to disease.
Consanguineous couples share significant segments of their DNA, increasing the odds that children may inherit two copies of disease-related mutations.
As a result, studies show increased rates of autosomal recessive disorders, congenital birth defects, intellectual disability, and early mortality among the offspring of consanguineous pairs compared to the general population.
Several studies have also found links between parental consanguinity and increased risk of complex psychiatric disorders like schizophrenia, bipolar disorder, and depression.
However, research on this association has been limited, especially in the Indian subcontinent where consanguineous marriage rates are high.
Studying a South India Population to Assess Schizophrenia Risk
To better understand the potential role of parental consanguinity in schizophrenia, researchers conducted a study in the rural South Indian region of Turuvekere.
Turuvekere is located in the Tumkur district of Karnataka state and has a predominantly Hindu population engaged in agriculture and related activities.
Consanguineous marriage is common in rural South India and regarded as a customary practice strengthening family ties.
The NIMHANS team recruited 120 schizophrenia patients and 222 healthy controls from the same villages and communities in Turuvekere.
This ensured that cases and controls came from a similar sociocultural background.
Evaluating Parental Consanguinity by Interviews & DNA Analysis
Researchers gathered three generations of family history for each participant using pedigree charts and a standardized family interview.
They asked specific questions to determine whether parents were blood relatives such as first cousins.
This clinical interview method identified consanguineous parents for 10.7% of schizophrenia patients and 7.25% of controls.
The difference was not statistically significant.
The team also estimated consanguinity using DNA analysis.
They calculated an inbreeding coefficient (F) for each participant based on runs of homozygosity in their genome.
The coefficient indicates the amount of DNA shared by an individual’s parents due to relatedness.
A coefficient of 0.0156 or higher was defined as positive for parental consanguinity, with parents sharing ancestry as close as second cousins or closer relatives.
DNA Evidence Reveals Increased Consanguinity in Schizophrenia Patients
While the clinical interviews did not show a significant difference in consanguinity rates, the DNA results told a different story.
The average inbreeding coefficient was significantly higher in schizophrenia patients compared to healthy controls.
Using the 0.0156 cut-off, 62.5% of patients had DNA evidence of parental consanguinity compared to only 48.6% of controls.
This was a statistically significant difference, even after stringent quality control measures were applied to the genetic data.
Patients showed greater amounts of shared parental DNA across varying degrees of incestuous relationships.
For example, more patients had first cousin equivalent (21.7% vs 16.7%) or closer uncle-niece equivalent relatedness (18.3% vs 9.9%).
Implications of Findings for Schizophrenia Genetics and Risk
This study provides strong evidence that parental consanguinity is associated with increased schizophrenia risk in a South Indian rural population where the practice is common.
Critics argue that previous studies linking psychiatric disorders to consanguinity have been limited by hospital-based sampling.
By recruiting patients and controls from the same villages, these findings avoid that bias.
Consanguinity appears to increase schizophrenia vulnerability via multiple rare recessive genetic factors.
Disease risk goes up when an individual inherits two copies of these variants through shared ancestry.
The results align with modern theories that small effects of many genes likely contribute to schizophrenia instead of single major genetic factors.
Further genome analysis can identify whether specific chromosomal segments are shared more in patients with a family history of consanguinity.
This may help pinpoint locations of causative variants.
Takeaways for Genetic Counseling and Public Health
While consanguineous marriage confers social benefits in communities where it is traditional, this study highlights some genetic risks requiring consideration.
Genetic counseling should educate prospective couples about potential health effects on offspring without dictating decisions.
Expanding genetics infrastructure to enable population screening and testing of recessive disease carriers would empower families to make informed choices.
Increasing genetic literacy and access to services can mitigate risks while respecting cultural practices.
At a public health level, these findings support initiatives to boost mental health awareness and care in rural areas.
Early intervention can improve schizophrenia outcomes where parental consanguinity raises background genetic susceptibility.
Research is still needed to clarify the disease mechanisms linking consanguinity and neuropsychiatric disorders.
References
- Study: Parental consanguinity among patients with schizophrenia in a rural community of South India: A clinical and genetic investigation
- Authors: Vikas Agarwal et al. (2021)
