精神分裂症、双相情感障碍和重度抑郁障碍的逻辑关系。第 4 部分:来自染色体 4 高密度关联筛查的证据。
A logical relationship for schizophrenia, bipolar, and major depressive disorder. Part 4: Evidence from chromosome 4 high-density association screen.
机构信息
Department of Radiology, Qianfo Hill Campus Hospital of Shandong University, Jinan 250061, Shandong, People's Republic of China.
Department of Medical Genetics, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, People's Republic of China.
出版信息
J Comp Neurol. 2019 Feb 1;527(2):392-405. doi: 10.1002/cne.24543. Epub 2018 Oct 31.
Convergent evidence from genetics, symptomatology, and psychopharmacology imply that there are intrinsic connections between schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD). Familial clustering of SCZ, BPD, and MDD was systematically investigated [Aukes et al. (2012); Genetics in Medicine 14(3): 338-341], and any two or even three of these disorders could co-exist in some families. A total of 56,134 SNPs on chromosome 4 were genotyped by Affymetrix Genome-Wide Human SNP array 6.0 on 119 SCZ, 253 BPD (Type-I), 177 MDD patients, and 1,000 controls in a relative homogenous population in China. Susceptibility genes on chromosome 4 for the three major psychiatric disorders were systematically identified including outstanding genes (CXCL13, FSTL5, GLRB, KCNIP4, LPHN3, MAPK10, NPFFR2, NSUN7, PCDH10, PCDH7, PPA2, PPARGC1A, SCD5, SCFD2, and UNC5C). Unexpectedly, flanking genes for up to 93.67% of the associated SNPs were also confirmed in an enlarged cohort of 986 SCZ patients. Taken all relevant evidence together, our chromosome 4 results implicate that both of bipolar and major depressive disorders might be subtypes of SCZ rather than independent disease entity. Furthermore, similar evidence was also observed on chromosome 3, 5, 6, 7, and 8 [2018; The Journal of Comparative Neurology 526(1):59-79; Chen et al. (2017); American Journal of Translational Research 9(5):2473-2491; Chen et al. (2016); Current Molecular Medicine, 16(9):840-854; Chen et al. (2015); Behavioural Brain Research, 293:241-51; Chen et al. (2016); Molecular Neurobiology, 54(8):5868-5882].
来自遗传学、症状学和精神药理学的综合证据表明,精神分裂症(SCZ)、双相情感障碍(BPD)和重度抑郁症(MDD)之间存在内在联系。已经系统地研究了 SCZ、BPD 和 MDD 的家族聚集性[Aukes 等人(2012 年);《遗传医学杂志》14(3):338-341],并且这些疾病中的任何两种甚至三种都可能存在于某些家庭中。在中国一个相对同质的人群中,对 119 例 SCZ、253 例 BPD(I 型)、177 例 MDD 患者和 1000 名对照者的染色体 4 上的 56134 个 SNP 进行了 Affymetrix Genome-Wide Human SNP 阵列 6.0 基因分型。系统地鉴定了染色体 4 上三种主要精神疾病的易感基因,包括突出基因(CXCL13、FSTL5、GLRB、KCNIP4、LPHN3、MAPK10、NPFFR2、NSUN7、PCDH10、PCDH7、PPA2、PPARGC1A、SCD5、SCFD2 和 UNC5C)。出乎意料的是,在 986 例 SCZ 患者的扩大队列中,多达 93.67%的相关 SNP 侧翼基因也得到了证实。综合所有相关证据,我们在染色体 4 上的结果表明,双相情感障碍和重度抑郁症可能都是精神分裂症的亚型,而不是独立的疾病实体。此外,在染色体 3、5、6、7 和 8 上也观察到了类似的证据[2018;《比较神经学杂志》526(1):59-79;Chen 等人(2017);《美国转化研究杂志》9(5):2473-2491;Chen 等人(2016);《当代分子医学》,16(9):840-854;Chen 等人(2015);《行为脑研究》,293:241-51;Chen 等人(2016);《分子神经生物学》,54(8):5868-5882]。