RORA rs8042149 polymorphism moderates the association between PTSD symptom severity and transverse temporal gyrus thickness in Han Chinese adults who lost their only child

Jul 25, 2022Journal of affective disorders

A Genetic Variant Influences the Link Between PTSD Severity and Hearing Area Thickness in Han Chinese Adults Who Lost Their Only Child

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Abstract

Significant genotype × PTSD symptom severity interaction effects were found for bilateral transverse temporal gyrus thickness.

Individuals with the homozygous T/T genotype showed a positive association between PTSD symptom severity and thickness of the bilateral transverse temporal gyrus.
For those with the heterozygous G/T genotype, PTSD symptom severity was negatively associated with the thickness of the left transverse temporal gyrus.
No significant effects were observed in any subcortical regions.
The findings suggest that the non-risk T/T genotype may play a protective role regarding temporal gyrus thickness in individuals experiencing PTSD.

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BACKGROUND: The G allele in retinoid-related orphan receptor alpha (RORA, rs8042149) gene is associated with post-traumatic stress disorder (PTSD) diagnosis and more severe symptoms, reported in the first genome-wide association study of PTSD and subsequent replication studies. Although recent MRI studies identified brain structural deficits in RORA rs8042149 risk G allele carriers, the neural mechanism underlying RORA-related brain structural changes in PTSD remains poorly understood.

METHODS: This study included 227 Han Chinese adults who lost their only child. Cortical thickness and subcortical volume were extracted using FreeSurfer, and PTSD severity was assessed using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to assess the interaction effect between RORA genotypes (T/T, G/T, and G/G) and PTSD severity on cortical and subcortical structures.

RESULTS: Significant genotype × PTSD symptom severity interaction effects were found for bilateral transverse temporal gyrus thickness. For individuals with the homozygous T/T genotype, current PTSD symptom severity was positively associated with bilateral transverse temporal gyrus thickness. For individuals with heterozygous G/T genotype, current PTSD symptom severity was negatively associated with the left transverse temporal gyrus thickness. No significant main or interaction effects were found in any subcortical regions.

LIMITATION: Cross-sectional design of this study.

CONCLUSION: These findings suggest that the non-risk T/T genotype - but not the risk G allele carriers - has a potentially protective or compensatory role on temporal gyrus thickness in adults who lost their only child. These results highlight the moderation effect of RORA polymorphism on the relationship between PTSD symptom severity and cortical structural changes.

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RORA rs8042149 polymorphism moderates the association between PTSD symptom severity and transverse temporal gyrus thickness in Han Chinese adults who lost their only child

Abstract

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