Causal relationship between hypothyroidism and peripheral neuropathy: a Mendelian randomization study of European ancestry

BackgroundMetabolic disorders are significant risk factors for peripheral neuropathy (PN) diseases. However, current clinical observational studies cannot fully determine the causal relationships between hypothyroidism (HT) and PN diseases.MethodsWe performed univariate Mendelian randomization (MR)...

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Main Authors: Xiping Duan, Tianchi Zhang, Ke Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2024.1436823/full
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author Xiping Duan
Tianchi Zhang
Ke Wang
author_facet Xiping Duan
Tianchi Zhang
Ke Wang
author_sort Xiping Duan
collection DOAJ
description BackgroundMetabolic disorders are significant risk factors for peripheral neuropathy (PN) diseases. However, current clinical observational studies cannot fully determine the causal relationships between hypothyroidism (HT) and PN diseases.MethodsWe performed univariate Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) associated with hypothyroidism and two diseases clinically presented as HT (autoimmune thyroid disease and benign neoplasm of the pituitary gland and craniopharyngeal duct) as instrumental variables. We selected eight peripheral neuropathy diseases (diabetic neuropathy, nerve root/plexus disorder, carpal tunnel syndrome, polyneuropathies, sciatica with lumbago, trigeminal neuralgia, postherpetic neuralgia, small fiber neuropathy) as outcomes. Genetic data were sourced from authoritative genome-wide association study (GWAS) datasets. We primarily used the inverse variance-weighted (IVW) method and conducted a comprehensive sensitivity analysis to ensure robustness.ResultsThe IVW results indicated that HT was significantly associated with an increased risk of diabetic peripheral neuropathy (OR = 1.22, p = 6.49E-05). HT was also significantly linked to nerve root/plexus disorder (OR = 1.04, p = 6.43E-06) and carpal tunnel syndrome (OR = 1.04, p = 0.004), but appeared to be a potential protective factor for polyneuropathies (OR = 0.93, p = 0.0009). Additionally, autoimmune thyroid disease (AITD) was identified as a potential risk factor for carpal tunnel syndrome (OR = 13.79, p = 0.006) and a protective factor for polyneuropathies (OR = 0.0011; p = 4.44E-5).ConclusionsThis study provides genetic evidence supporting potential causal links between hypothyroidism and various peripheral neuropathy diseases.
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spelling doaj-art-0368de95d68e47c8a7cdef668f5e2be92024-11-27T04:33:11ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-11-011510.3389/fendo.2024.14368231436823Causal relationship between hypothyroidism and peripheral neuropathy: a Mendelian randomization study of European ancestryXiping Duan0Tianchi Zhang1Ke Wang2Acupuncture Anaesthesia Clinical Research Institute, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLaboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaAcupuncture Anaesthesia Clinical Research Institute, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaBackgroundMetabolic disorders are significant risk factors for peripheral neuropathy (PN) diseases. However, current clinical observational studies cannot fully determine the causal relationships between hypothyroidism (HT) and PN diseases.MethodsWe performed univariate Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) associated with hypothyroidism and two diseases clinically presented as HT (autoimmune thyroid disease and benign neoplasm of the pituitary gland and craniopharyngeal duct) as instrumental variables. We selected eight peripheral neuropathy diseases (diabetic neuropathy, nerve root/plexus disorder, carpal tunnel syndrome, polyneuropathies, sciatica with lumbago, trigeminal neuralgia, postherpetic neuralgia, small fiber neuropathy) as outcomes. Genetic data were sourced from authoritative genome-wide association study (GWAS) datasets. We primarily used the inverse variance-weighted (IVW) method and conducted a comprehensive sensitivity analysis to ensure robustness.ResultsThe IVW results indicated that HT was significantly associated with an increased risk of diabetic peripheral neuropathy (OR = 1.22, p = 6.49E-05). HT was also significantly linked to nerve root/plexus disorder (OR = 1.04, p = 6.43E-06) and carpal tunnel syndrome (OR = 1.04, p = 0.004), but appeared to be a potential protective factor for polyneuropathies (OR = 0.93, p = 0.0009). Additionally, autoimmune thyroid disease (AITD) was identified as a potential risk factor for carpal tunnel syndrome (OR = 13.79, p = 0.006) and a protective factor for polyneuropathies (OR = 0.0011; p = 4.44E-5).ConclusionsThis study provides genetic evidence supporting potential causal links between hypothyroidism and various peripheral neuropathy diseases.https://www.frontiersin.org/articles/10.3389/fendo.2024.1436823/fullhypothyroidismperipheral neuropathycarpal tunnel syndromepolyneuropathiesMendelian randomizationcausal relationship
spellingShingle Xiping Duan
Tianchi Zhang
Ke Wang
Causal relationship between hypothyroidism and peripheral neuropathy: a Mendelian randomization study of European ancestry
Frontiers in Endocrinology
hypothyroidism
peripheral neuropathy
carpal tunnel syndrome
polyneuropathies
Mendelian randomization
causal relationship
title Causal relationship between hypothyroidism and peripheral neuropathy: a Mendelian randomization study of European ancestry
title_full Causal relationship between hypothyroidism and peripheral neuropathy: a Mendelian randomization study of European ancestry
title_fullStr Causal relationship between hypothyroidism and peripheral neuropathy: a Mendelian randomization study of European ancestry
title_full_unstemmed Causal relationship between hypothyroidism and peripheral neuropathy: a Mendelian randomization study of European ancestry
title_short Causal relationship between hypothyroidism and peripheral neuropathy: a Mendelian randomization study of European ancestry
title_sort causal relationship between hypothyroidism and peripheral neuropathy a mendelian randomization study of european ancestry
topic hypothyroidism
peripheral neuropathy
carpal tunnel syndrome
polyneuropathies
Mendelian randomization
causal relationship
url https://www.frontiersin.org/articles/10.3389/fendo.2024.1436823/full
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AT kewang causalrelationshipbetweenhypothyroidismandperipheralneuropathyamendelianrandomizationstudyofeuropeanancestry