PheWAS of a Polygenic Predictor of Thyroid Function

NCT03597659 | Completed

• 1 other identifier: CIC1421-18-09
• Study Type: observational
• Target: 37,154
• Locations: 1 country
• Sites: 1

Brief Summary

Performing a phenome-wide association study (PheWAS) identifying clinical diagnoses associated with a polygenic predictor of Thyroid stimulating hormone (TSH) levels identified by a previously published genome-wide association study (GWAS). PheWAS will be applied in an electronic-health-record (EHR) cohort including North American (n: 37,154) and European participants using 1,318 phenotypes.

Conditions

Thyroid; Genetic Predisposition to Disease

Outcome Measures

Primary Outcomes (1)

• thyroid disorders associated with a polygenic predictor of thyroid stimulating hormone levels

  All relevants statisticals associations between a defined polygenic predictor of TSH and thyroids disorders

  population inclued in the eMERGE Phase I & II Network or BioVU resource until 1 july 2018

Secondary Outcomes (1)

• Clinical diagnoses associated with a polygenic predictor of TSH levels

  population inclued in the eMERGE Phase I & II Network or BioVU resource until 1 july 2018

Study Arms (1)

BioVU-Emerge EHR cohort

A primary EHR population derived from the eMERGE Phase I \& II Network (n=16,924), a consortium of medical centers using EHRs as a tool for genomic research, and from Vanderbilt University Medical Center's (VUMC) BioVU resource (n=20,230). BioVU is VUMC's de-identified collection of patients whose DNA was extracted from discarded blood and linked to phenotypes through a de-identified EHR. All subjects were born prior to 1990 and fell within 4 standard deviations for each of the first 2 principal components based on common single nucleotide variants (SNVs) for the subset of subjects self-identified as "White, non-Hispanic".

Genetic: phenome-wide association study (PheWAS)

Interventions

phenome-wide association study (PheWAS) GENETIC

Phenome-wide association study (PheWAS) identifying clinical diagnoses associated with a polygenic predictor of TSH levels identified by a previously published genome-wide association study (GWAS) which included North American and European participants. A phenome-wide scanning of 1,318 phenotypes will be performed, using a cohort of 37,154 North American individuals of European ancestry with electronic-health-record (EHR) data.

BioVU-Emerge EHR cohort

Eligibility Criteria

• Age: 28 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

A primary electronic health record population derived from the eMERGE Phase I \& II Network (n=16,924), and from Vanderbilt University Medical Center's (VUMC) BioVU resource (n=20,230). All subjects born prior to 1990 and falling within 4 standard deviations for each of the first 2 principal components based on common single nucleotide variants (SNVs) for the subset of subjects self-identified as "White, non-Hispanic". Thyroid Stimulating Hormone(TSH)-Population subgroup: Subjects of European Ancestry in BioVU who did not have any ICD-9 or ICD-10 codes for thyroid diseases and who had thyroid stimulating hormone (TSH) measurements that fell within the clinically normal reference range.

You may qualify if:

• Being part of the eMERGE Phase I \& II Network
• Being part of the BioVU resource
• Falling within 4 standard deviations for each of the first 2 principal components based on common single nucleotide variants (SNVs) for the subset of subjects self-identified as "White, non-Hispanic"

You may not qualify if:

• born after 1990

Sponsors & Collaborators

• Groupe Hospitalier Pitie-Salpetriere: lead
• Vanderbilt University Medical Center: collaborator

Study Sites (1)

AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM

Paris, 75013, France

Location

Related Publications (1)

• Salem JE, Shoemaker MB, Bastarache L, Shaffer CM, Glazer AM, Kroncke B, Wells QS, Shi M, Straub P, Jarvik GP, Larson EB, Velez Edwards DR, Edwards TL, Davis LK, Hakonarson H, Weng C, Fasel D, Knollmann BC, Wang TJ, Denny JC, Ellinor PT, Roden DM, Mosley JD. Association of Thyroid Function Genetic Predictors With Atrial Fibrillation: A Phenome-Wide Association Study and Inverse-Variance Weighted Average Meta-analysis. JAMA Cardiol. 2019 Feb 1;4(2):136-143. doi: 10.1001/jamacardio.2018.4615.

  PMID: 30673079 BACKGROUND

MeSH Terms

Conditions

Thyroid Diseases; Genetic Predisposition to Disease

Condition Hierarchy (Ancestors)

Endocrine System Diseases; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant director, clinical investigation center Paris Est

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: July 24, 2018
• Study Start: September 1, 2017
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: September 26, 2019

Record last verified: 2019-09

Locations

FR (1)