J Clin Endocrinol Metab. 2022 Oct 20:dgac614. doi: 10.1210/clinem/dgac614. Online ahead of print.
ABSTRACT
INTRODUCTION: Systemic lupus erythematosus (SLE) and hypothyroidism often coexist in observational studies; however, the causal relationship between them remains controversial.
METHODS: Complementary genetic approaches, including genetic correlation, Mendelian randomization (MR) and colocalization analysis, were conducted to assess the potential causal association between SLE and primary hypothyroidism using summary statistics from large-scale genome-wide association studies (GWASs). The association between SLE and thyroid-stimulating hormone (TSH) was further analyzed to help interpret the findings. In addition, findings were verified using a validation dataset, as well as through different MR methods with different model assumptions.
RESULTS: The linkage disequilibrium score regression revealed a shared genetic structure between SLE and primary hypothyroidism, with the significant genetic correlation estimated to be 0.2488 (p = 6.00 × 10-4). MR analysis with the inverse variance weighted (IVW) method demonstrated a bidirectional causal relationship between SLE and primary hypothyroidism. The odds ratio (OR) of SLE on primary hypothyroidism was 1.037 (95% CI, 1.013-1.061; p = 2.00 × 10-3) and that of primary hypothyroidism on SLE was 1.359 (95% CI, 1.217-1.520; p < 0.001). The OR of SLE on TSH was 1.007 (95% CI, 1.001-1.013; p = 0.032) .However, TSH was not causally associated with SLE (p = 0.152). Similar results were found using different MR methods. In addition, colocalization analysis suggested that shared causal variants existed between SLE and primary hypothyroidism. The results of the validation analysis indicated a bidirectional causal relationship between SLE and primary hypothyroidism, as well as shared loci.
CONCLUSION: In summary, a bidirectional causal relationship between SLE and primary hypothyroidism was observed with complementary genetic approaches.
PMID:36263677 | DOI:10.1210/clinem/dgac614
