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Meta-Analysis
. 2020 Jun 30;10(1):209.
doi: 10.1038/s41398-020-00902-6.

Multi-trait analysis for genome-wide association study of five psychiatric disorders

Yulu Wu #  1   2 , Hongbao Cao #  3 , Ancha Baranova #  4   5 , Hailiang Huang  6   7 , Sheng Li  8 , Lei Cai  8 , Shuquan Rao  9 , Minhan Dai  1   2 , Min Xie  1   2 , Yikai Dou  1   2 , Qinjian Hao  10 , Ling Zhu  1   2 , Xiangrong Zhang  11 , Yin Yao  12 , Fuquan Zhang  13 , Mingqing Xu  14   15 , Qiang Wang  16   17
Affiliations
Meta-Analysis

Multi-trait analysis for genome-wide association study of five psychiatric disorders

Yulu Wu et al. Transl Psychiatry. .

Erratum in

Abstract

We conducted a cross-trait meta-analysis of genome-wide association study on schizophrenia (SCZ) (n = 65,967), bipolar disorder (BD) (n = 41,653), autism spectrum disorder (ASD) (n = 46,350), attention deficit hyperactivity disorder (ADHD) (n = 55,374), and depression (DEP) (n = 688,809). After the meta-analysis, the number of genomic loci increased from 14 to 19 in ADHD, from 3 to 10 in ASD, from 45 to 57 in DEP, from 8 to 54 in BD, and from 64 to 87 in SCZ. We observed significant enrichment of overlapping genes among different disorders and identified a panel of cross-disorder genes. A total of seven genes were found being commonly associated with four out of five psychiatric conditions, namely GABBR1, GLT8D1, HIST1H1B, HIST1H2BN, HIST1H4L, KCNB1, and DCC. The SORCS3 gene was highlighted due to the fact that it was involved in all the five conditions of study. Analysis of correlations unveiled the existence of two clusters of related psychiatric conditions, SCZ and BD that were separate from the other three traits, and formed another group. Our results may provide a new insight for genetic basis of the five psychiatric disorders.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Manhattan plots of GWAS and MTAG results.
The left and right panels display GWAS and MTAG results, respectively. The X-axis is the chromosomal position, and the Y-axis is negative log10 transformed P-values for each SNP. The red line indicates genome-wide significance (P = 5 × 10–8). Green diamonds indicate an independent genome-wide significant association (lead SNP). Blue points show SNPs in LD with lead SNPs.
Fig. 2
Fig. 2. Significant genes and SORCS3’s correlation with the five disorders.
a Chromosomal ideograms for significant genes of MTAG results. Chromosomal locations containing significant genes of different phenotypes are annotated in different colors. The phenotype circles were arranged in a proximity algorithm. b Biological pathways between the SORCS3 gene and the five disorders.
Fig. 3
Fig. 3. Genetic correlations and path diagram of genomic structural equation modeling (SEM) of the five disorders.
The left and right panels display GWAS and MTAG results, respectively. a Genetic correlations between five psychiatric disorders. Line width is proportional to genetic correlations between five psychiatric disorders. The numbers show rgs amongst the five disorders. b Path diagram of genomic SEM and exploratory factor analysis (EFA) analyses of the five disorders in the GWAS and MTAG results. The values were standardized results of confirmatory factor analysis.
Fig. 4
Fig. 4. Sub-network enrichment analysis (SNEA) results of the eight genes.
Each of the item identified from SNEA associated with at least two common genes.
See this image and copyright information in PMC

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