Whole-exome sequencing identifies variants associated with structural MRI markers in patients with bipolar disorders
| Autor: | Eunsoo Won, Woo Suk Tae, Byung Joo Ham, Mi Ryung Han, June Kang, Yunjung Cho, Kyu Man Han, Wooyoung Kang, Youbin Kang, Aram Kim |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Bipolar Disorder Uncinate fasciculus Neuroimaging Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide White matter 03 medical and health sciences Nerve Fibers 0302 clinical medicine Exome Sequencing medicine Humans SNP Bipolar disorder Gray Matter Exome sequencing Genetics Genome Human Superior longitudinal fasciculus Cadherins medicine.disease White Matter 030227 psychiatry Psychiatry and Mental health Clinical Psychology Diffusion Tensor Imaging medicine.anatomical_structure Female Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Journal of Affective Disorders. 249:159-168 |
| ISSN: | 0165-0327 |
| DOI: | 10.1016/j.jad.2019.02.028 |
| Popis: | s Background Bipolar disorder (BD) is one of the most heritable psychiatric disorders. A growing number of whole-exome sequencing (WES) studies for BD has been performed, however, no research has examined the association between single nucleotide variants (SNVs) from WES and structural magnetic resonance imaging (MRI) data. Methods We sequenced whole-exomes in 53 patients with BD and 82 healthy control participants at an initial discovery stage and investigated the impacts of SNVs in risk genes from WES analysis on the cortical gray-matter thickness and integrity of white matter tracts and in the following stage. Cortical thickness and white matter integrity were investigated using the FreeSurfer and TRACULA (Tracts Constrained by UnderLying Anatomy). Results We identified 122 BD-related genes including KMT2C, AHNAK, CDH23, DCHS1, FRAS1, MACF1 and RYR3 and observed 27 recurrent copy number alteration regions including gain on 8p23.1 and loss on 15q11.1 - q11.2. Among them, single nucleotide polymorphism (SNP) rs4639425 in KMT2C gene, which regulates histone H3 lysine 4 (H3K4) methylation involved in chromatin remodeling, was associated with widespread alterations of white matter integrity including the cingulum, uncinate fasciculus, cortico-spinal tract, and superior longitudinal fasciculus. Limitation The small sample size of patients with BD in the genome data may cause our study to be underpowered when searching for putative rare mutations. Conclusion This study first combined a WES approach and neuroimaging findings in psychiatric disorders. We postulate the rs4639425 may be associated with BD-related microstructural changes of white matter tracts. |
| Databáze: | OpenAIRE |
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