Skip to main content

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

Publication ,  Journal Article
Ye, Z; Mayer, J; Ivacic, L; Zhou, Z; He, M; Schrodi, SJ; Page, D; Brilliant, MH; Hebbring, SJ
Published in: Eur J Hum Genet
April 2015

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.

Duke Scholars

Published In

Eur J Hum Genet

DOI

EISSN

1476-5438

Publication Date

April 2015

Volume

23

Issue

4

Start / End Page

523 / 529

Location

England

Related Subject Headings

  • Reproducibility of Results
  • Proteins
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Macular Degeneration
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Genetic Predisposition to Disease
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ye, Z., Mayer, J., Ivacic, L., Zhou, Z., He, M., Schrodi, S. J., … Hebbring, S. J. (2015). Phenome-wide association studies (PheWASs) for functional variants. Eur J Hum Genet, 23(4), 523–529. https://doi.org/10.1038/ejhg.2014.123
Ye, Zhan, John Mayer, Lynn Ivacic, Zhiyi Zhou, Min He, Steven J. Schrodi, David Page, Murray H. Brilliant, and Scott J. Hebbring. “Phenome-wide association studies (PheWASs) for functional variants.Eur J Hum Genet 23, no. 4 (April 2015): 523–29. https://doi.org/10.1038/ejhg.2014.123.
Ye Z, Mayer J, Ivacic L, Zhou Z, He M, Schrodi SJ, et al. Phenome-wide association studies (PheWASs) for functional variants. Eur J Hum Genet. 2015 Apr;23(4):523–9.
Ye, Zhan, et al. “Phenome-wide association studies (PheWASs) for functional variants.Eur J Hum Genet, vol. 23, no. 4, Apr. 2015, pp. 523–29. Pubmed, doi:10.1038/ejhg.2014.123.
Ye Z, Mayer J, Ivacic L, Zhou Z, He M, Schrodi SJ, Page D, Brilliant MH, Hebbring SJ. Phenome-wide association studies (PheWASs) for functional variants. Eur J Hum Genet. 2015 Apr;23(4):523–529.

Published In

Eur J Hum Genet

DOI

EISSN

1476-5438

Publication Date

April 2015

Volume

23

Issue

4

Start / End Page

523 / 529

Location

England

Related Subject Headings

  • Reproducibility of Results
  • Proteins
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Macular Degeneration
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Genetic Predisposition to Disease