Unknown

Dataset Information

0

Phenome-wide association studies (PheWASs) for functional variants.


ABSTRACT: The genome-wide association study (GWAS) is a powerful approach for studying the genetic complexities of human disease. Unfortunately, GWASs often fail to identify clinically significant associations and describing function can be a challenge. GWAS is a phenotype-to-genotype approach. It is now possible to conduct a converse genotype-to-phenotype approach using extensive electronic medical records to define a phenome. This approach associates a single genetic variant with many phenotypes across the phenome and is called a phenome-wide association study (PheWAS). The majority of PheWASs conducted have focused on variants identified previously by GWASs. This approach has been efficient for rediscovering gene-disease associations while also identifying pleiotropic effects for some single-nucleotide polymorphisms (SNPs). However, the use of SNPs identified by GWAS in a PheWAS is limited by the inherent properties of the GWAS SNPs, including weak effect sizes and difficulty when translating discoveries to function. To address these challenges, we conducted a PheWAS on 105 presumed functional stop-gain and stop-loss variants genotyped on 4235 Marshfield Clinic patients. Associations were validated on an additional 10?640 Marshfield Clinic patients. PheWAS results indicate that a nonsense variant in ARMS2 (rs2736911) is associated with age-related macular degeneration (AMD). These results demonstrate that focusing on functional variants may be an effective approach when conducting a PheWAS.

SUBMITTER: Ye Z 

PROVIDER: S-EPMC4666492 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

2015-01-01 | S-EPMC4481696 | BioStudies
2014-01-01 | S-EPMC3904236 | BioStudies
2016-01-01 | S-EPMC5035188 | BioStudies
2018-01-01 | S-EPMC5789733 | BioStudies
2020-01-01 | S-EPMC7003082 | BioStudies
2013-01-01 | S-EPMC3969265 | BioStudies
2016-01-01 | S-EPMC4718547 | BioStudies
2015-01-01 | S-EPMC4661230 | BioStudies
2018-01-01 | S-EPMC5985339 | BioStudies
2018-01-01 | S-EPMC6191429 | BioStudies