Individuals with schizophrenia experience fractures at rates significantly exceeding those of the general populace, a phenomenon that has confounded medical professionals for many years. Common explanations often attribute this to adverse medication effects, inadequate nutrition, or insufficient sunlight exposure. However, a recent genomic study indicates that the true answer may lie within DNA shared by both conditions.
A team of researchers, spearheaded by Feng Liu at Tianjin Medical University General Hospital, uncovered 195 genetic loci that are concurrently linked to schizophrenia and bone mineral density. This work, published on January 6 in Genomic Psychiatry, scrutinized data from over half a million subjects and disclosed that the identical genetic variants that impact brain circuitry also influence skeletal robustness.
The relationship is not uniform. Heel bone density displayed the most substantial correlation with schizophrenia, sharing 140 genetic loci. Other bone regions, such as the lumbar spine and femoral neck, exhibited weaker associations. Notably, forearm bone density showed no overlapping signals, although researchers mentioned that this could be due to a scarcity of data for that particular site instead of a genuine absence.
When Brain Chemistry Meets Bone Structure
Both schizophrenia and osteoporosis are polygenic; this means that numerous genetic variants each contribute slightly to risk rather than a single gene determining the result. The inquiry was whether any variants coincided.
The team implemented a multilevel genomic strategy to scrutinize shared signals throughout the complete genome, within specific chromosomal areas, and at individual variant locations. This approach identified connections even when the same genetic alteration influenced the two conditions in different ways.
Those 195 loci corresponded to 1,376 protein-coding genes, many clustered within pathways related to nitrogen compound metabolism and anatomical growth. In practical terms, the molecular machinery responsible for processing neurotransmitters in the brain seems to also construct collagen frameworks in bone.
“As both disorders are highly polygenic and may share biological pathways, investigating their shared genetic base could assist in elucidating the mechanisms that contribute to their comorbidity,” explains Feng Liu.
Effects varied widely. Only approximately one-fifth to two-thirds of the shared variants influenced schizophrenia and bone traits in the same manner. Many variants that heightened psychiatric risk simultaneously reduced bone density, offering a direct molecular rationale for the increased fracture rates observed in patients.
A Patchwork Rather Than a Pattern
The diverse effect directions aid in understanding why previous genome-wide studies discovered weak correlations despite a significant genetic overlap. Earlier methodologies averaged across all variants, obscuring underlying complexities.
This is clinically relevant as it demonstrates that the association between mental disorders and skeletal diseases isn’t governed by a single pathway. Rather, it reflects a tapestry of shared genetic influences that manifest differently depending on tissue type and skeletal region.
Should certain genetic variants heighten susceptibility to bone deterioration in schizophrenia patients, they may gain from earlier screening or preventive oversight. Upcoming polygenic risk scores could help identify which individuals require more vigilant monitoring of their skeletal health.
The analysis has its limitations. All data originated from individuals of European descent, and rare variants or gene-environment interactions were not captured. Nonetheless, the scale provides one of the clearest depictions to date of how psychiatric and physical health can intersect on a genetic level.
These findings recontextualize an enduring clinical issue. Fragile bones in individuals with schizophrenia may not solely be a side effect of treatment or a consequence of lifestyle. They may represent an additional manifestation of the same fundamental biology, quietly unfolding in another area of the body.
Genomic Psychiatry: [10.61373/gp026a.0012](https://doi.org/10.61373/gp026a.0012)
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