Sex-different interrelationships of rs945270, cerebral gray matter volumes, and attention deficit hyperactivity disorder: a region-wide study across brain
机构：[1]Beijing Huilongguan Hospital, Peking University Huilongguan Clinical School of Medicine, Beijing 100096, China[2]Department of Psychiatry, Yale University School of Medicine,New Haven, CT 06510, USA[3]Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China[4]Laboratory of RadiationOncology and Radiobiology, Fujian Medical University Cancer Hospital and Fujian Cancer Hospital, Fuzhou 350014, China[5]Shanghai Mental Health Center, Shanghai 200030,China[6]Department of Neurology, Shanghai Tongren Hospital, Shanghai Jiao Tong University, Shanghai 200080, China[7]Tianjin Mental Health Center, Tianjin 300222, China[8]Department of Psychiatry, the Second Xiangya Hospital, Central South University.The China National Clinical Research Center for Mental Health Disorders.National TechnologyInstitute of Psychiatry.Key Laboratory of Psychiatry and Mental Health of Hunan Province, Changsha 410017, China[9]Department of Neuroscience, Yale University School ofMedicine, New Haven, CT 06510, USA[10]Wu Tsai Institute, Yale University, New Haven, CT 06510, USA
Previous genome-wide association studies (GWAS) reported that the allele C of rs945270 of the kinectin 1 gene (KTN1) most significantly increased the gray matter volume (GMV) of the putamen and modestly regulated the risk for attention deficit hyperactivity disorder (ADHD). On the other hand, ADHD is known to be associated with a reduction in subcortical and cortical GMVs. Here, we examined the interrelationships of the GMVs, rs945270 alleles, and ADHD symptom scores in the same cohort of children. With data of rs945270 genotypes, GMVs of 118 brain regions, and ADHD symptom scores of 3372 boys and 3129 girls of the Adolescent Brain Cognition Development project, we employed linear regression analyses to examine the pairwise correlations adjusted for the third of the three traits and other relevant covariates, and examine their mediation effects. We found that the major allele C of rs945270 modestly increased risk for ADHD in males only when controlling for the confounding effects of the GMV of any one of the 118 cerebral regions (0.026 <= p <= 0.059: Top two: left and right putamen). This allele also significantly increased putamen GMV in males alone (left p = 2.8 x 10(-5), and right p = 9.4 x 10(-5); alpha = 2.1 x 10(-4)) and modestly increased other subcortical and cortical GMVs in both sexes (alpha < p < 0.05), whether or not adjusted for ADHD symptom scores. Both subcortical and cortical GMVs were significantly or suggestively reduced in ADHD when adjusted for rs945270 alleles, each more significantly in females (3.6 x 10(-7) <= p < alpha; Top two: left pallidum and putamen) and males (3.5 x 10(-6) <= p < alpha), respectively. Finally, the left and right putamen GMVs reduced 14.0% and 11.7% of the risk effects of allele C on ADHD, and allele C strengthened 4.5% (left) and 12.2% (right) of the protective effects of putamen GMVs on ADHD risk, respectively. We concluded that the rs945270-GMVs-ADHD relationships were sex-different. In males, the major allele C of rs945270 increased risk for ADHD, which was compromised by putamen GMVs; this allele also but only significantly increased putamen GMVs that then significantly protected against ADHD risk. In females, the top two GMVs significantly decreasing ADHD risk were left pallidum and putamen GMVs. Basal ganglia the left putamen in particular play the most critical role in the pathogenesis of ADHD.
第一作者机构：[1]Beijing Huilongguan Hospital, Peking University Huilongguan Clinical School of Medicine, Beijing 100096, China[2]Department of Psychiatry, Yale University School of Medicine,New Haven, CT 06510, USA
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推荐引用方式(GB/T 7714)：
Xingguang Luo,Wenhua Fang,Xiandong Lin,et al.Sex-different interrelationships of rs945270, cerebral gray matter volumes, and attention deficit hyperactivity disorder: a region-wide study across brain[J].TRANSLATIONAL PSYCHIATRY.2022,12(1):doi:10.1038/s41398-022-02007-8.
APA：
Xingguang Luo,Wenhua Fang,Xiandong Lin,Xiaoyun Guo,Yu Chen...&Chiang-Shan R. Li.(2022).Sex-different interrelationships of rs945270, cerebral gray matter volumes, and attention deficit hyperactivity disorder: a region-wide study across brain.TRANSLATIONAL PSYCHIATRY,12,(1)
MLA：
Xingguang Luo,et al."Sex-different interrelationships of rs945270, cerebral gray matter volumes, and attention deficit hyperactivity disorder: a region-wide study across brain".TRANSLATIONAL PSYCHIATRY 12..1(2022)
医学