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Dissecting the association between psychiatric disorders and neurological proteins: A genetic correlation and two-sample bidirectional Mendelian Randomization study
The role of neurological proteins in the development of bipolar disorder (BD) and schizophrenia (SCZ) remains elusive now. The current study aims to explore the potential genetic correlations of plasma neurological proteins with BD and SCZ.
By using the latest genome-wide association study (GWAS) summary data of BD and SCZ (including 41,917 BD cases, 11,260 SCZ cases and 396,091 controls) derived from the Psychiatric GWAS Consortium website (PGC) and a recently released GWAS of neurological proteins (including 750 individuals), we performed a linkage disequilibrium score regression (LDSC) analysis to detect the potential genetic correlations between the two common psychiatric disorders and each of the 92 neurological proteins. Two-sample Mendelian randomization (MR) analysis was then applied to assess the bidirectional causal relationship between the neurological proteins identified by LDSC and BD, SCZ.
LDSC analysis identified one neurological protein, NEP, which shown suggestive genetic correlation signals for both BD (coefficient = -0.165, P value = 0.035) and SCZ (coefficient= -0.235, P value = 0.020). However, those association did not remain significant after strict Bonferroni correction. Two sample MR analysis found that there was an association between genetically predicted level of NEP protein and BD (odd ratio [OR] = 0.87, P value = 1.61×10-6), SCZ (OR = 0.90, P value = 4.04 ×10-6). However, in the opposite direction, there is no genetically predicted association between BD, SCZ and NEP protein level.
This study provided novel clues for understanding the genetic effects of neurological proteins on BD and SCZ.