Genome-wide copy number variation-, validation- and screening study implicates a new copy number polymorphism associated with suicide attempts in major depressive disorder

Rao，Shitao1; Shi，Mai2; Han，Xinyu3; Ho Bun Lam，Marco4; Tong Chien，Wai5; Zhou，Keying6; Liu，Guangming3; Kwok Wing，Yun4; So，Hon Cheong7; Miu Yee Waye，Mary5

2020-06-15

10.1016/j.gene.2020.144901

GENE   影响因子和分区

0378-1119

1879-0038

BACKGROUND: The genetic basis of suicide attempts (SA) remained unclear, especially for the copy number variations (CNVs) involved. The present study aimed to identify the susceptibility variants associated with SA among Chinese people with major depressive disorder (MDD), covering both CNVs and single-nucleotide polymorphisms. METHODS: We conducted GWAS on MDD patients with or without SA and top results were tested in a replication study. A genome-wide CNV study was also performed. Subsequently, a validation assay using qRT-PCR technology was performed to confirm any associated CNV and then applied to the entire cohort to examine the association. RESULTS: Although GWAS did not identify any SNPs reaching genome-wide significance, we identified TPH2 as the top susceptibility gene (p-value=2.75e-05) in gene-based analysis, which is a strong biological candidate for its role in the serotonergic system. As for CNV analysis, we found that the global rate of CNV was higher in SA than that in non-SA subjects (p-value=0.023). The genome-wide CNV study revealed a SA-associated CNV region that achieved genome-wide significance (corrected p-value=0.014). The associated CNV was successfully validated with a more rigorous qRT-PCR assay and identified to be a common variant in this cohort. Its deletion rate was higher in SA subjects [OR=2.05 (1.02-4.12), adjusted p-value=0.045]. Based on the GTEx database, genetic variants that probed this CNV were significantly associated with the expression level of ZNF33B in two brain regions (p-value<4.2e-05). In stratified analysis, the CNV showed a significant effect [OR=2.58 (1.06-6.27), p-value=0.039] in those with high neuroticism but not in those with average or low neuroticism. CONCLUSIONS: We identified a new common CNV likely involving in the etiology of SA. This finding sheds light on an important role of the common CNVs in the understanding of genetic basis of SA, suggesting a new promising avenue for investigating the SA's genetic architecture.

genome-wide copy number variation study GWAS qRT-PCR assay SA

SCI

英语

其他

Government of the Hong Kong Special Administration Region (HMRF)[12131101][03144526]

Genetics & Heredity

Genetics & Heredity

WOS:000555786400008

ELSEVIER

MOLECULAR BIOLOGY & GENETICS

2-s2.0-85086716054

Scopus

1.The Nethersole School of Nursing, The Croucher Laboratory for Human Genomics, China; Department of Psychiatry, N.T, Hong Kong SAR, China
2.School of Biomedical Sciences,Faculty of Medicine,Chinese University of Hong Kong,Hong Kong SAR,China
3.College of Food and Biological Engineering,Jimei University,Xiamen,China
4.Department of Psychiatry,Hong Kong SAR,China
5.Nethersole School of Nursing,Croucher Laboratory for Human Genomics,China
6.Shenzhen people's hospital,2nd clinical medical college of Jinan University,1st affiliated hospital of Southern University of Science and Technology,Shenzhen,China
7.School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, N.T, Hong Kong SAR, China; KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Kunming Institute of Zoology and The Chinese University of Hong Kong, China; CUHK Shenzhen Research Institute, Shenzhen, China; Brain and Mind Institute, The Chinese University of Hong Kong, Hong Kong SAR, China

Rao，Shitao,Shi，Mai,Han，Xinyu,et al. Genome-wide copy number variation-, validation- and screening study implicates a new copy number polymorphism associated with suicide attempts in major depressive disorder[J]. GENE,2020,755.

Rao，Shitao.,Shi，Mai.,Han，Xinyu.,Ho Bun Lam，Marco.,Tong Chien，Wai.,...&Miu Yee Waye，Mary.(2020).Genome-wide copy number variation-, validation- and screening study implicates a new copy number polymorphism associated with suicide attempts in major depressive disorder.GENE,755.

Rao，Shitao,et al."Genome-wide copy number variation-, validation- and screening study implicates a new copy number polymorphism associated with suicide attempts in major depressive disorder".GENE 755(2020).