Genetic Association and Mendelian Randomization for Hypothyroidism Highlight Immune Molecular Mechanisms

Overview

Journal iScience

Publisher Cell Press

Date 2022 Sep 12

PMID 36093044

Authors

Samuel Mathieu

Mewen Briend

Erik Abner

Christian Couture

Zhonglin Li

Yohan Bosse

Sebastien Theriault

Tonu Esko

Benoit J Arsenault

Patrick Mathieu

Affiliations

Soon will be listed here.

Abstract

We carried out a genome-wide association analysis including 51,194 cases of hypothyroidism and 443,383 controls. In total, 139 risk loci were associated to hypothyroidism with genes involved in lymphocyte function. Candidate genes associated with hypothyroidism were identified by using molecular quantitative trait loci, colocalization, and enhancer-promoter chromatin looping. Mendelian randomization (MR) identified 42 blood expressed genes and circulating proteins as candidate causal molecules in hypothyroidism. Drug-gene interaction analysis provided evidence that immune checkpoint and tyrosine kinase inhibitors used in cancer therapy increase the risk of hypothyroidism. Hence, integrative mapping and MR support that expression of genes and proteins enriched in lymphocyte function are associated with the risk of hypothyroidism and provide genetic evidence for drug-induced hypothyroidism and identify actionable potential drug targets.

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