PheWAS of a Polygenic Predictor of Thyroid Function (PHETHYR)

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.

Study Overview

• Status: Completed
• Conditions: Genetic Predisposition to Disease; Thyroid
• Intervention / Treatment: Genetic: phenome-wide association study (PheWAS)

Detailed Description

Applying a genetic predictor of thyroid stimulating hormone levels to an electronic-health-record cohort to verify associations with thyroid disorders as positive controls, and identify new associations .

• Study Type: Observational
• Enrollment (Actual): 37154

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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.

Description

Inclusion Criteria:

• 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"

Exclusion Criteria:

• born after 1990

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical diagnoses associated with a polygenic predictor of TSH levels	All relevants statisticals associations between a defined polygenic predictor of thyroid stimulating hormone and clinical diagnoses	population inclued in the eMERGE Phase I & II Network or BioVU resource until 1 july 2018

Collaborators and Investigators

• Sponsor: Groupe Hospitalier Pitie-Salpetriere
• Collaborators: Vanderbilt University Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2017
• Primary Completion (ACTUAL): July 1, 2018
• Study Completion (ACTUAL): July 1, 2018

Study Registration Dates

• First Submitted: July 13, 2018
• First Submitted That Met QC Criteria: July 13, 2018
• First Posted (ACTUAL): July 24, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 26, 2019
• Last Update Submitted That Met QC Criteria: September 24, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Disease Attributes; Thyroid Diseases; Disease Susceptibility; Genetic Predisposition to Disease
• Other Study ID Numbers: CIC1421-18-09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No