Department of Preventive Medicine, School of Medicine, Eulji University, Daejeon, Republic of Korea.
Department of Biomedical Informatics, School of Medicine, Konyang University, Daejeon, Republic of Korea.
J Affect Disord. 2024 Sep 15;361:97-103. doi: 10.1016/j.jad.2024.05.152. Epub 2024 Jun 2.
Multiple genes might interact to determine the age at onset of bipolar disorder. We investigated gene-gene interactions related to age at onset of bipolar disorder in the Korean population, using genome-wide association study (GWAS) data.
The study population consisted of 303 patients with bipolar disorder. First, the top 1000 significant single-nucleotide polymorphisms (SNPs) associated with age at onset of bipolar disorder were selected through single SNP analysis by simple linear regression. Subsequently, the QMDR method was used to find gene-gene interactions.
The best 10 SNPs from simple regression were located in chromosome 1, 2, 3, 10, 11, 14, 19, and 21. Only five SNPs were found in several genes, such as FOXN3, KIAA1217, OPCML, CAMSAP2, and PTPRS. On QMDR analyses, five pairs of SNPs showed significant interactions with a CVC exceeding 1/5 in a two-locus model. The best interaction was found for the pair of rs60830549 and rs12952733 (CVC = 1/5, P < 1E-07). In three-locus models, four combinations of SNPs showed significant associations with age at onset, with a CVC of >1/5. The best three-locus combination was rs60830549, rs12952733, and rs12952733 (CVC = 2/5, P < 1E-6). The SNPs showing significant interactions were located in the KIAA1217, RBFOX3, SDK2, CYP19A1, NTM, SMYD3, and RBFOX1 genes.
Our analysis confirmed genetic interactions influencing the age of onset for bipolar disorder and identified several potential candidate genes. Further exploration of the functions of these promising genes, which may have multiple roles within the neuronal network, is necessary.
多个基因可能相互作用，共同决定双相情感障碍的发病年龄。我们利用全基因组关联研究（GWAS）的数据，在韩国人群中研究了与双相情感障碍发病年龄相关的基因-基因相互作用。
研究人群包括 303 名双相情感障碍患者。首先，通过简单线性回归的单 SNP 分析，选择与双相情感障碍发病年龄相关的前 1000 个显著单核苷酸多态性（SNP）。随后，使用 QMDR 方法寻找基因-基因相互作用。
简单回归的前 10 个最佳 SNP 位于染色体 1、2、3、10、11、14、19 和 21 上。只有 5 个 SNP 位于 FOXN3、KIAA1217、OPCML、CAMSAP2 和 PTPRS 等几个基因中。在 QMDR 分析中，在双 SNP 模型中，有 5 对 SNP 表现出显著的相互作用，CVC 超过 1/5。最佳相互作用是 rs60830549 和 rs12952733 之间的相互作用（CVC=1/5，P<1E-07）。在三 SNP 模型中，有四个 SNP 组合与发病年龄显著相关，CVC>1/5。最佳三 SNP 组合为 rs60830549、rs12952733 和 rs12952733（CVC=2/5，P<1E-6）。表现出显著相互作用的 SNP 位于 KIAA1217、RBFOX3、SDK2、CYP19A1、NTM、SMYD3 和 RBFOX1 基因中。
我们的分析证实了影响双相情感障碍发病年龄的遗传相互作用，并确定了几个潜在的候选基因。有必要进一步探索这些有前途的基因的功能，这些基因可能在神经元网络中具有多种作用。
