Tingfu Du1, Shuquan Rao1, Lin Wu1, Ning Ye1, Zeyue Liu1, Huiling Hu1, Jianbo Xiu1, Yan Shen1, Qi Xu2. 1. National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing 100005, China. 2. National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing 100005, China. Electronic address: xuqi@pumc.edu.cn.
Abstract
BACKGROUND: Major depressive disorder (MDD) is a common, chronic and recurrent mental disease but the precise mechanism behind this disorder remains unknown. FTO is one of the N6-methyladenosine (m6A) modification genes and has recently been found to be associated with depression. N6-methyladenosine (m6A) is the most abundant internal modification on RNA, which is highly enriched within the brain. There are five genes involved in m6A modification including FTO, but whether these m6A modification genes could confer a risk of MDD is still unclear. This study aimed to investigate the genetic influence of the m6A modification genes on risk of MDD. METHODS: We genotyped 23 SNPs in 5 modification genes among 738 patients with MDD and 1098 controls. The UNPHASED program was applied to analyze the genotyping data for allelic and genotypic association with MDD. RESULTS: Of the 23 SNPs selected, rs12936694 from the m6A demethylase gene ALKBH5 showed allelic association (χ(2)=11.19, p=0.0008, OR=1.491, 95%CI 1.179-1.887) and genotypic association (χ(2)=12.26, df=2, p=0.0022) with MDD. LIMITATIONS: Replication and functional study are required to draw a firm conclusion. CONCLUSIONS: The ALKBH5 gene may play a role in conferring risk of MDD in the Chinese population.
BACKGROUND:Major depressive disorder (MDD) is a common, chronic and recurrent mental disease but the precise mechanism behind this disorder remains unknown. FTO is one of the N6-methyladenosine (m6A) modification genes and has recently been found to be associated with depression. N6-methyladenosine (m6A) is the most abundant internal modification on RNA, which is highly enriched within the brain. There are five genes involved in m6A modification including FTO, but whether these m6A modification genes could confer a risk of MDD is still unclear. This study aimed to investigate the genetic influence of the m6A modification genes on risk of MDD. METHODS: We genotyped 23 SNPs in 5 modification genes among 738 patients with MDD and 1098 controls. The UNPHASED program was applied to analyze the genotyping data for allelic and genotypic association with MDD. RESULTS: Of the 23 SNPs selected, rs12936694 from the m6A demethylase gene ALKBH5 showed allelic association (χ(2)=11.19, p=0.0008, OR=1.491, 95%CI 1.179-1.887) and genotypic association (χ(2)=12.26, df=2, p=0.0022) with MDD. LIMITATIONS: Replication and functional study are required to draw a firm conclusion. CONCLUSIONS: The ALKBH5 gene may play a role in conferring risk of MDD in the Chinese population.
Authors: Kelsie J Faulds; Jennifer N Egelston; Laura J Sedivy; Matthew K Mitchell; Sanjana Garimella; Hanna Kozlowski; Angelo D'Alessandro; Kirk C Hansen; Jeremy L Balsbaugh; Christopher J Phiel Journal: J Biol Chem Date: 2018-05-18 Impact factor: 5.157