title: The SEMA5A gene is associated with hippocampal volume, and their interaction is associated with performance on Raven's Progressive Matrices.
abstract: The Allen Brain Atlas shows that the semaphorin 5A (SEMA5A) gene, which encodes an important protein for neurogenesis and neuronal apoptosis, is predominantly expressed in the human hippocampus. Structural and functional neuroimaging studies have further shown that the hippocampus plays an important role in the performance on Raven's Progressive Matrices (RPM), a measure of reasoning ability and general fluid intelligence. Thus far, however, no study has examined the relationships between the SEMA5A gene polymorphism, hippocampal volume, and RPM performance. The current study collected both structural MRI, genetic, and behavioral data in 329 healthy Chinese adults, and examined associations between SEMA5A variants, hippocampal volume, and performance on RAPM (the advanced form of RPM). After controlling for intracranial volume (ICV), sex, and age, SEMA5A genetic polymorphism at the SNP rs42352 had the strongest association with hippocampal volume (p=0.00000552 and 0.000103 for right and left hippocampal volumes, respectively), with TT homozygotes having higher hippocampal volume than the other genotypes. Furthermore, there was a high correlation between right hippocampal volume and RAPM performance (r=0.42, p=0.0000509) for SEMA5A rs42352 TT homozygotes. This study provides the first evidence for the involvement of the SEMA5A gene in hippocampal structure and their interaction on RAPM performance. Future studies of the hippocampus-RPM associations should consider genetic factors as potential moderators.
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, China.
authors.forename: Bi
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Psychology and Social Behavior, University of California, Irvine, CA, USA. Electronic address: cschen@uci.edu.
authors.forename: Chuansheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, China.
authors.forename: Gui
authors.initials: G
authors.lastname: Xue
authors.affiliation: Department of Biological Chemistry and Institute of Genomics and Bioinformatics, University of California, Irvine, CA, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Moyzis
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, China. Electronic address: psydongqi@126.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: He
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
authors.forename: Yunxin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
authors.forename: Chongde
authors.initials: C
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D006801:Humans; D007360:Intelligence / Q000235:genetics / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D039961:Semaphorins; D013850:Thinking / Q000502:physiology*; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C491228:SEMA5A protein, human; D039961:Semaphorins
keywords: Hippocampal volume; Raven's Progressive Matrices; Semaphorin 5A gene