TY - JOUR
T1 - Genome-wide association study identified INSC gene associated with Trail Making Test Part A and Alzheimer's disease related cognitive phenotypes
AU - The Alzheimer's Disease Neuroimaging Initiative
AU - Wang, Kesheng
AU - Xu, Chun
AU - Smith, Amanda
AU - Xiao, Danqing
AU - Navia, R. Osvaldo
AU - Lu, Yongke
AU - Xie, Changchun
AU - Piamjariyakul, Ubolrat
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/12/20
Y1 - 2021/12/20
N2 - Background: The Trail Making Test (TMT) Part A (TMT-A) is a good measure of performance on cognitive processing speed. This study aimed to perform a genome-wide association study of TMT-A in Alzheimer's disease (AD). Methods: A total of 757 individuals with TMT-A phenotypes and 620,901 single nucleotide polymorphisms (SNPs) were extracted from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) cohort. AD related cognitive phenotypes include TMT-A, TMT-B, Functional Activities Questionnaire (FAQ), Clinical Dementia Rating Sum of Boxes (CDR-SB), and Alzheimer's Disease Assessment Scale–Cognitive Subscale 13 (ADAS13). Multivariable linear regression analysis of TMT-A was conducted using PLINK software. The most TMT-A associated gene was tested with Color Trails Test 1 Form A (CTTA), a culturally fair analog of the TMT-A. Functional annotation of SNPs was performed using the RegulomeDB and Genotype-Tissue Expression (GTEx) databases. Results: The best signal with TMT-A was rs1108010 (p = 4.34 × 10−8) at 11p15.2 within INSC gene, which was also associated with TMT-B, FAQ, CDR-SB, and ADAS13 (p = 2.47 × 10−4, 8.56 × 10−3, 0.0127 and 0.0188, respectively). Furthermore, suggestive loci were identified such as FOXD2 and CLTA with TMT-A, GBP1/GBP3 with TMT-B, GRIK2 with FAQ, BAALC and CCDC146 with CDR-SB, BAALC and NKAIN2 with ADAS13. Additionally, the best SNP within INSC associated with CTTA was rs7931705 (p = 6.15 × 10−5). Several SNPs had significant eQTLs using GTEx. Conclusions: We identified several genes/loci associated with TMT-A and AD related phenotypes. These findings offer the potential for new insights into the pathogenesis of cognitive function and Alzheimer's disease.
AB - Background: The Trail Making Test (TMT) Part A (TMT-A) is a good measure of performance on cognitive processing speed. This study aimed to perform a genome-wide association study of TMT-A in Alzheimer's disease (AD). Methods: A total of 757 individuals with TMT-A phenotypes and 620,901 single nucleotide polymorphisms (SNPs) were extracted from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) cohort. AD related cognitive phenotypes include TMT-A, TMT-B, Functional Activities Questionnaire (FAQ), Clinical Dementia Rating Sum of Boxes (CDR-SB), and Alzheimer's Disease Assessment Scale–Cognitive Subscale 13 (ADAS13). Multivariable linear regression analysis of TMT-A was conducted using PLINK software. The most TMT-A associated gene was tested with Color Trails Test 1 Form A (CTTA), a culturally fair analog of the TMT-A. Functional annotation of SNPs was performed using the RegulomeDB and Genotype-Tissue Expression (GTEx) databases. Results: The best signal with TMT-A was rs1108010 (p = 4.34 × 10−8) at 11p15.2 within INSC gene, which was also associated with TMT-B, FAQ, CDR-SB, and ADAS13 (p = 2.47 × 10−4, 8.56 × 10−3, 0.0127 and 0.0188, respectively). Furthermore, suggestive loci were identified such as FOXD2 and CLTA with TMT-A, GBP1/GBP3 with TMT-B, GRIK2 with FAQ, BAALC and CCDC146 with CDR-SB, BAALC and NKAIN2 with ADAS13. Additionally, the best SNP within INSC associated with CTTA was rs7931705 (p = 6.15 × 10−5). Several SNPs had significant eQTLs using GTEx. Conclusions: We identified several genes/loci associated with TMT-A and AD related phenotypes. These findings offer the potential for new insights into the pathogenesis of cognitive function and Alzheimer's disease.
KW - Alzheimer's disease
KW - Cognitive functioning
KW - Genome-wide association study
KW - INSC
KW - Trail making test
KW - eQTLs
UR - http://www.scopus.com/inward/record.url?scp=85110337157&partnerID=8YFLogxK
U2 - 10.1016/j.pnpbp.2021.110393
DO - 10.1016/j.pnpbp.2021.110393
M3 - Article
C2 - 34224794
AN - SCOPUS:85110337157
SN - 0278-5846
VL - 111
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
M1 - 110393
ER -