TY - JOUR
T1 - EQTLs weighted genetic correlation analysis detected brain region differences in genetic correlations for complex psychiatric disorders
AU - Wen, Yan
AU - Zhang, Feng
AU - Ma, Xiancang
AU - Fan, Qianrui
AU - Wang, Wenyu
AU - Xu, Jiawen
AU - Zhu, Feng
AU - Hao, Jingcan
AU - He, Awen
AU - Liu, Li
AU - Liang, Xiao
AU - Du, Yanan
AU - Li, Ping
AU - Wu, Cuiyan
AU - Wang, Sen
AU - Wang, Xi
AU - Ning, Yujie
AU - Guo, Xiong
N1 - Publisher Copyright:
© The Author(s) 2018.
PY - 2019/5
Y1 - 2019/5
N2 - Background: Psychiatric disorders are usually caused by the dysfunction of various brain regions. Incorporating the genetic information of brain regions into correlation analysis can provide novel clues for pathogenetic and therapeutic studies of psychiatric disorders. Methods: The latest genome-wide association study (GWAS) summary data of schizophrenia (SCZ), bipolar disorder (BIP), autism spectrum disorder (AUT), major depression disorder (MDD), and attention-deficit/hyperactivity disorder (ADHD) were obtained from the Psychiatric GWAS Consortium (PGC). The expression quantitative trait loci (eQTLs) datasets of 10 brain regions were driven from the genotype-tissue expression (GTEx) database. The PGC GWAS summaries were first weighted by the GTEx eQTLs summaries for each brain region. Linkage disequilibrium score regression was applied to the weighted GWAS summary data to detect genetic correlation for each pair of 5 disorders. Results: Without considering brain region difference, significant genetic correlations were observed for BIP vs SCZ (P = 1.68 × 10-63), MDD vs SCZ (P = 5.08 × 10-45), ADHD vs MDD (P = 1.93 × 10-44), BIP vs MDD (P = 6.39 × 10-9), AUT vs SCZ (P = .0002), and ADHD vs SCZ (P = .0002). Utilizing brain region related eQTLs weighted LD score regression, different strengths of genetic correlations were observed within various brain regions for BIP vs SCZ, MDD vs SCZ, ADHD vs MDD, and SCZ vs ADHD. For example, the most significant genetic correlations were observed at anterior cingulate cortex (P = 1.13 × 10-34) for BIP vs SCZ. Conclusions: This study provides new clues for elucidating the mechanism of genetic correlations among various psychiatric disorders.
AB - Background: Psychiatric disorders are usually caused by the dysfunction of various brain regions. Incorporating the genetic information of brain regions into correlation analysis can provide novel clues for pathogenetic and therapeutic studies of psychiatric disorders. Methods: The latest genome-wide association study (GWAS) summary data of schizophrenia (SCZ), bipolar disorder (BIP), autism spectrum disorder (AUT), major depression disorder (MDD), and attention-deficit/hyperactivity disorder (ADHD) were obtained from the Psychiatric GWAS Consortium (PGC). The expression quantitative trait loci (eQTLs) datasets of 10 brain regions were driven from the genotype-tissue expression (GTEx) database. The PGC GWAS summaries were first weighted by the GTEx eQTLs summaries for each brain region. Linkage disequilibrium score regression was applied to the weighted GWAS summary data to detect genetic correlation for each pair of 5 disorders. Results: Without considering brain region difference, significant genetic correlations were observed for BIP vs SCZ (P = 1.68 × 10-63), MDD vs SCZ (P = 5.08 × 10-45), ADHD vs MDD (P = 1.93 × 10-44), BIP vs MDD (P = 6.39 × 10-9), AUT vs SCZ (P = .0002), and ADHD vs SCZ (P = .0002). Utilizing brain region related eQTLs weighted LD score regression, different strengths of genetic correlations were observed within various brain regions for BIP vs SCZ, MDD vs SCZ, ADHD vs MDD, and SCZ vs ADHD. For example, the most significant genetic correlations were observed at anterior cingulate cortex (P = 1.13 × 10-34) for BIP vs SCZ. Conclusions: This study provides new clues for elucidating the mechanism of genetic correlations among various psychiatric disorders.
KW - Brain regions
KW - Expression quantitative trait loci
KW - Genetic correlation
KW - Genomewide association studies
KW - Linkage disequilibrium score regression
KW - Psychiatric disorders
UR - https://www.scopus.com/pages/publications/85072058728
U2 - 10.1093/schbul/sby080
DO - 10.1093/schbul/sby080
M3 - 文章
C2 - 29912442
AN - SCOPUS:85072058728
SN - 0586-7614
VL - 45
SP - 709
EP - 715
JO - Schizophrenia Bulletin
JF - Schizophrenia Bulletin
IS - 3
ER -
