A Genome-Wide Association Study Identifies Genetic Variants Associated with Mathematics Ability.
Mathematics ability is a complex cognitive trait with polygenic heritability. Genome-wide association study (GWAS) has been an effective approach to investigate genetic components underlying mathematic ability. Although previous studies reported several candidate genetic variants, none of them exceeded genome-wide significant threshold in general populations. Herein, we performed GWAS in Chinese elementary school students to identify potential genetic variants associated with mathematics ability. The discovery stage included 494 and 504 individuals from two independent cohorts respectively. The replication stage included another cohort of 599 individuals. In total, 28 of 81 candidate SNPs that met validation criteria were further replicated. Combined meta-analysis of three cohorts identified four SNPs (rs1012694, rs11743006, rs17778739 and rs17777541) of SPOCK1 gene showing association with mathematics ability (minimum p value 5.67 × 10-10, maximum β -2.43). The SPOCK1 gene is located on chromosome 5q31.2 and encodes a highly conserved glycoprotein testican-1 which was associated with tumor progression and prognosis as well as neurogenesis. This is the first study to report genome-wide significant association of individual SNPs with mathematics ability in general populations. Our preliminary results further supported the role of SPOCK1 during neurodevelopment. The genetic complexities underlying mathematics ability might contribute to explain the basis of human cognition and intelligence at genetic level.
Center for Neurogenetics, Shenzhen Institute of Neuroscience, Shenzhen, 518057, China.|State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, 102206, China.
Huan
H
Chen
Department of Healthy Management, Research Institute of Surgery, DaPing Hospital, Third Military Medical University, Chongqing, 400042, China.
Xiao-Hong
XH
Gu
CapitalBio eHealth Science &Technology (Beijing) Co., Ltd., Beijing, 102206, China.|National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, China.
Yuxi
Y
Zhou
CapitalBio eHealth Science &Technology (Beijing) Co., Ltd., Beijing, 102206, China.|National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, China.
Zeng
Z
Ge
CapitalBio eHealth Science &Technology (Beijing) Co., Ltd., Beijing, 102206, China.|National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, China.
Bin
B
Wang
Department of Linguistics, The University of Hong Kong, Hong Kong, China.
Wai Ting
WT
Siok
CapitalBio eHealth Science &Technology (Beijing) Co., Ltd., Beijing, 102206, China.|National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, China.
Guoqing
G
Wang
Department of Anatomy, The University of Hong Kong, Hong Kong, China.
Michael
M
Huen
The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, China.
Yuyang
Y
Jiang
Center for Neurogenetics, Shenzhen Institute of Neuroscience, Shenzhen, 518057, China.|School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, China.
Li-Hai
LH
Tan
CapitalBio eHealth Science &Technology (Beijing) Co., Ltd., Beijing, 102206, China.|National Engineering Research Center for Beijing Biochip Technology, Beijing, 102206, China.|The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, China.|Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing, 100084, China.
Yimin
Y
Sun
D015331:Cohort Studies; D055106:Genome-Wide Association Study; D006801:Humans; D008433:Mathematics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results