MAPT haplotype-stratified GWAS reveals differential association for AD risk variants.

ABSTRACT:

Introduction

MAPT H1 haplotype is implicated as a risk factor for neurodegenerative diseases including Alzheimer's disease (AD).

Methods

Using Alzheimer's Disease Genetics Consortium (ADGC) genome-wide association study (GWAS) data (n = 18,841), we conducted a MAPT H1/H2 haplotype-stratified association to discover MAPT haplotype-specific AD risk loci.

Results

We identified 11 loci-5 in H2-non-carriers and 6 in H2-carriers-although none of the MAPT haplotype-specific associations achieved genome-wide significance. The most significant H2 non-carrier-specific association was with a NECTIN2 intronic (P = 1.33E-07) variant, and that for H2 carriers was near NKX6-1 (P = 1.99E-06). The GABRG2 locus had the strongest epistasis with MAPT H1/H2 variant rs8070723 (P = 3.91E-06

SUBMITTER: Strickland SL 

PROVIDER: S-EPMC7983911 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature