Association of the major depressive disorder-associated locus rs12415800 with bipolar disorder in a Taiwan Biobank-NHIRD linked cohort.

Abstract

Background: Genome-wide association studies in East Asian populations have identified the gene variant, rs12415800, of the Sirtuin 1 gene (SIRT1) as a major depressive disorder (MDD) risk locus with the A allele conferring increased risk. Accumulating evidence suggests that SIRT1-related genetic effects extend beyond MDD.

Aims: To investigate the association between rs12415800 and bipolar disorder, with additional analysis of MDD.

Method: We analysed data from the Taiwan Biobank linked to the National Health Insurance Research Database, including 145 780 participants of Han Chinese ancestry. Clinically diagnosed bipolar disorder and MDD were identified using standardised ICD-9-CM and ICD-10-CM codes. Multivariable logistic regression models were applied with the GG genotype as the reference, adjusting for age and sex. Stratified analyses were conducted by age group and sex.

Results: Both the rs12415800 AG and AA genotypes were associated with an increased risk of bipolar disorder. Compared with GG genotype carriers, AA genotype carriers had a significantly higher risk of bipolar disorder overall (adjusted odds ratio (aOR) = 1.20, 95% CI = 1.05-1.37), particularly among participants aged ≥50 years (aOR = 1.38, 95% CI = 1.14-1.68). The overall and age-stratified associations remained materially similar after excluding participants with schizophrenia or schizo-affective disorder, although sex-specific findings were inconsistent.

Conclusions: Our findings suggest that genetic variation near SIRT1, particularly the rs12415800 risk A allele, may be associated with bipolar disorder susceptibility, especially among older individuals. Given prior evidence linking this allele to reduced SIRT1 mRNA expression, further investigation of SIRT1-related pathways in the pathophysiology of bipolar disorder is warranted.