Skip to main content
Journal cover image

Reported environmental exposures are inversely associated with obtaining a genetic diagnosis in the Undiagnosed Diseases Network.

Publication ,  Journal Article
Silverman, EK; Allard, P; Loscalzo, J; Mulvihill, JJ; Korrick, SA; Undiagnosed Diseases Network,
Published in: Am J Med Genet A
June 2019

The Undiagnosed Diseases Network (UDN) aims to achieve a unifying etiologic diagnosis for patients with mysterious conditions. Although the UDN has focused on the identification of genetic determinants, environmental etiologies may be causative or modifying agents that interact with predisposing genes. We developed and implemented a screening questionnaire to assess environmental exposures in UDN patients. We hypothesized that patients with potentially adverse environmental exposures would be less likely to have a genetic basis for their undiagnosed disease. Among seven postnatal environmental exposure categories assessed in 269 UDN participants, patients with a confirmed or strong candidate genetic diagnosis were significantly less likely to report exposures to metals, dust, or chemicals (p < 0.05). A composite variable of the seven exposure categories was substantially more common (40%) in patients without a genetic diagnosis than in those with a genetic diagnosis (18.4%) (p = 0.004). In multivariable analysis adjusting for age and sex, the composite variable of any positive environmental exposure was associated with a reduced odds of finding a genetic diagnosis (OR 0.41, 95% CI 0.18-0.96, p = 0.04). These results were generally robust to exclusion of patients with early life disease onset. Our results suggest a possible approach to increase the yield of genetic etiologies for adult undiagnosed diseases by first focusing on patients without significant environmental exposures. Still, there is ample reason to expect cases in which specific environmental exposures impact the risk of clinically evident genetic disease. Our findings emphasize the importance of systematic investigations of potential environmental risk factors for undiagnosed diseases.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Am J Med Genet A

DOI

EISSN

1552-4833

Publication Date

June 2019

Volume

179

Issue

6

Start / End Page

958 / 965

Location

United States

Related Subject Headings

  • Young Adult
  • Whole Genome Sequencing
  • Undiagnosed Diseases
  • Surveys and Questionnaires
  • Risk Factors
  • Rare Diseases
  • Male
  • Humans
  • Genetic Testing
  • Genetic Predisposition to Disease
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Silverman, E. K., Allard, P., Loscalzo, J., Mulvihill, J. J., Korrick, S. A., & Undiagnosed Diseases Network, . (2019). Reported environmental exposures are inversely associated with obtaining a genetic diagnosis in the Undiagnosed Diseases Network. Am J Med Genet A, 179(6), 958–965. https://doi.org/10.1002/ajmg.a.61132
Silverman, Edwin K., Patrick Allard, Joseph Loscalzo, John J. Mulvihill, Susan A. Korrick, and Susan A. Undiagnosed Diseases Network. “Reported environmental exposures are inversely associated with obtaining a genetic diagnosis in the Undiagnosed Diseases Network.Am J Med Genet A 179, no. 6 (June 2019): 958–65. https://doi.org/10.1002/ajmg.a.61132.
Silverman EK, Allard P, Loscalzo J, Mulvihill JJ, Korrick SA, Undiagnosed Diseases Network. Reported environmental exposures are inversely associated with obtaining a genetic diagnosis in the Undiagnosed Diseases Network. Am J Med Genet A. 2019 Jun;179(6):958–65.
Silverman, Edwin K., et al. “Reported environmental exposures are inversely associated with obtaining a genetic diagnosis in the Undiagnosed Diseases Network.Am J Med Genet A, vol. 179, no. 6, June 2019, pp. 958–65. Pubmed, doi:10.1002/ajmg.a.61132.
Silverman EK, Allard P, Loscalzo J, Mulvihill JJ, Korrick SA, Undiagnosed Diseases Network. Reported environmental exposures are inversely associated with obtaining a genetic diagnosis in the Undiagnosed Diseases Network. Am J Med Genet A. 2019 Jun;179(6):958–965.
Journal cover image

Published In

Am J Med Genet A

DOI

EISSN

1552-4833

Publication Date

June 2019

Volume

179

Issue

6

Start / End Page

958 / 965

Location

United States

Related Subject Headings

  • Young Adult
  • Whole Genome Sequencing
  • Undiagnosed Diseases
  • Surveys and Questionnaires
  • Risk Factors
  • Rare Diseases
  • Male
  • Humans
  • Genetic Testing
  • Genetic Predisposition to Disease