TY - JOUR
T1 - Negative Results: A genome-wide association study of plasma phosphorylated tau181
AU - Aarsland, Dag
AU - Hye, Abdul
AU - Ashton, Nicholas
PY - 2021/4/21
Y1 - 2021/4/21
N2 - Plasma phosphorylated tau at threonine-181 (P-tau181) demonstrates promise as an accessible blood-based biomarker specific to Alzheimer’s Disease (AD), with levels recently demonstrating high predictive accuracy for AD-relevant pathology. The genetic underpinnings of P-tau181 levels, however, remain elusive. This study presents the first genome-wide association study of plasma P-tau181 in a total sample of 1,153 participants from two independent cohorts. No loci, other than those within the APOE genomic region (lead variant=rs429358, beta=0.32, p=8.44x10-25) demonstrated association with P-tau181 at genome-wide significance (p<5x10-08), though rs60872856 on chromosome 2 came close (beta=-0.28, p=3.23x10-07, nearest gene=CYTIP). As the APOE 4 allele is already a well-established genetic variant associated with AD, this study found no evidence of novel genetic associations relevant to plasma P-tau181, though presents rs60872856 on chromosome 2 as a candidate locus to be further evaluated in future larger size GWAS.
AB - Plasma phosphorylated tau at threonine-181 (P-tau181) demonstrates promise as an accessible blood-based biomarker specific to Alzheimer’s Disease (AD), with levels recently demonstrating high predictive accuracy for AD-relevant pathology. The genetic underpinnings of P-tau181 levels, however, remain elusive. This study presents the first genome-wide association study of plasma P-tau181 in a total sample of 1,153 participants from two independent cohorts. No loci, other than those within the APOE genomic region (lead variant=rs429358, beta=0.32, p=8.44x10-25) demonstrated association with P-tau181 at genome-wide significance (p<5x10-08), though rs60872856 on chromosome 2 came close (beta=-0.28, p=3.23x10-07, nearest gene=CYTIP). As the APOE 4 allele is already a well-established genetic variant associated with AD, this study found no evidence of novel genetic associations relevant to plasma P-tau181, though presents rs60872856 on chromosome 2 as a candidate locus to be further evaluated in future larger size GWAS.
M3 - Article
SN - 0197-4580
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -