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A significant, functional and replicable risk KTN1 variant block for schizophrenia

التفاصيل البيبلوغرافية
العنوان: A significant, functional and replicable risk KTN1 variant block for schizophrenia
المؤلفون: Qiao Mao, Xiandong Lin, Qin Yin, Ping Liu, Yong Zhang, Shihao Qu, Jianying Xu, Wenhong Cheng, Xinqun Luo, Longli Kang, Reyisha Taximaimaiti, Chengchou Zheng, Huihao Zhang, Xiaoping Wang, Honggang Ren, Yuping Cao, Jie Lin, Xingguang Luo
المصدر: Scientific Reports, Vol 13, Iss 1, Pp 1-13 (2023)
بيانات النشر: Nature Portfolio, 2023.
سنة النشر: 2023
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Abstract Cortical and subcortical structural alteration has been extensively reported in schizophrenia, including the unusual expansion of gray matter volumes (GMVs) of basal ganglia (BG), especially putamen. Previous genome-wide association studies pinpointed kinectin 1 gene (KTN1) as the most significant gene regulating the GMV of putamen. In this study, the role of KTN1 variants in risk and pathogenesis of schizophrenia was explored. A dense set of SNPs (n = 849) covering entire KTN1 was analyzed in three independent European- or African-American samples (n = 6704) and one mixed European and Asian Psychiatric Genomics Consortium sample (n = 56,418 cases vs. 78,818 controls), to identify replicable SNP-schizophrenia associations. The regulatory effects of schizophrenia-associated variants on the KTN1 mRNA expression in 16 cortical or subcortical regions in two European cohorts (n = 138 and 210, respectively), the total intracranial volume (ICV) in 46 European cohorts (n = 18,713), the GMVs of seven subcortical structures in 50 European cohorts (n = 38,258), and the surface areas (SA) and thickness (TH) of whole cortex and 34 cortical regions in 50 European cohorts (n = 33,992) and eight non-European cohorts (n = 2944) were carefully explored. We found that across entire KTN1, only 26 SNPs within the same block (r2 > 0.85) were associated with schizophrenia across ≥ 2 independent samples (7.5 × 10–5 ≤ p ≤ 0.048). The schizophrenia-risk alleles, which increased significantly risk for schizophrenia in Europeans (q 0.05), and (4) the TH of eight regional cortices potentially (0.006 ≤ p ≤ 0.050; q > 0.05), and consistently decreased (1) the BG GMVs significantly (1.8 × 10–19 ≤ p ≤ 0.050; q
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-023-27448-z
URL الوصول: https://doaj.org/article/53aaa15cc194415fba7f5952d03f83a4
رقم الأكسشن: edsdoj.53aaa15cc194415fba7f5952d03f83a4
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20452322
DOI:10.1038/s41598-023-27448-z