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Dissecting the association between psychiatric disorders and neurological proteins: a genetic correlation and two-sample bidirectional Mendelian randomization study

Published online by Cambridge University Press:  28 March 2022

Huimei Huang ,
Shiqiang Cheng Open the ORCID record for Shiqiang Cheng [Opens in a new window] ,
Chun’e Li ,
Bolun Cheng ,
Li Liu ,
Xuena Yang ,
Peilin Meng ,
Yao Yao ,
Chuyu Pan  and
Jingxi Zhang
...Show all authors
Huimei Huang
Affiliation:
Department of Nephrology, Xi’an Children’s Hospital, The Affiliated Children’s Hospital of Xi’an Jiaotong University, Xi’an, China
Shiqiang Cheng
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Chun’e Li
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Bolun Cheng
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Li Liu
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Xuena Yang
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Peilin Meng
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Yao Yao
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Chuyu Pan
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Jingxi Zhang
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Huijie Zhang
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Yujing Chen
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Zhen Zhang
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Yan Wen
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Yumeng Jia
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Feng Zhang*
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
*
Author for correspondence: Feng Zhang, Email: [email protected]
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Abstract

Objectives:

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.

Methods:

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 randomisation (MR) analysis was then applied to assess the bidirectional causal relationship between the neurological proteins identified by LDSC, BD and SCZ.

Results:

LDSC analysis identified one neurological protein, NEP, which shows 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, BD (odd ratio [OR] = 0.87, p value = 1.61 × 10−6) and 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.

Conclusion:

This study provided novel clues for understanding the genetic effects of neurological proteins on BD and SCZ.

Keywords

bipolar disorderschizophrenialinkage disequilibrium score regressionneurological proteingenetic correlation
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 34 , Issue 6 , December 2022 , pp. 311 - 317
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Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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Footnotes

Huimei Huang and Shiqiang Cheng contributed equally to this work and share first authorship.

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