Erratum: Whole-genome sequence-based analysis of thyroid function

Taylor, Peter N.; Porcu, Eleonora; Chew, Shelby; Campbell, Purdey J; Traglia, Michela; Brown, Suzanne J.; Mullin, Benjamin H.; Shihab, Hashem A.; Min, Josine L.; Walter, Klaudia; Memari, Yasin; Jie, Huang; Barnes, Michael R.; Beilby, John; Charoen, Pimphen; Danecek, Petr; Dudbridge, Frank; Forgetta, Vincenzo; Greenwood, Celia; Grundberg, Elin; Johnson, Andrew D.; Hui, Jennie; Lim, Ee Mun; McCarthy, Shane; Muddyman, Dawn; Panicker, Vijay; Perry, John; Bell, Jordana T.; Yuan, Wei; Relton, Caroline; Gaunt, Tom R.; Schlessinger, David; Abecasis, Gonçalo; Cucca, Francesco; Surdulescu, Gabriela L.; Woltersdorf, Wolfram; Zeggini, Eleftheria; Zheng, Hou-Feng; Toniolo, Daniela; Dayan, Colin; Naitza, Silvia; Walsh, John P.; Spector, Tim D.; Smith, George Davey; Durbin, Richard; Richards, J. Brent; Soranzo, Nicole; Timpson, Nicholas J.; Wilson, Scott G.

doi:10.1038/ncomms8172

Cited by 13 publications

(13 citation statements)

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“…Rrs3184504 at SH2B3 (encoding SH2B adaptor protein 3), neighboring and in high linkage disequilibrium (LD) (R 2 > 0.9) with rs653178 at ATXN2, is highly pleiotropic and also associated with systolic and diastolic blood pressure, fibrinogen, red and white cell traits, platelet count, and cardiovascular disease, strongly suggesting the potential to affect kidney function through mechanisms other than thyroid function (68). Rs2396084 near VEGFA was strongly associated with both TSH in the reference range and hypothyroidism in previous GWAS (41,42), and was also GWAS significant for decreased eGFR crea , decreased eGFR cys , risk of CKD, and decreased UACR after accounting for multiple testing (49,52,53), and therefore unsuitable as an MR instrument as revealed by the MR-PRESSO analysis. It is possible that variation at the VEGFA locus influences vascular development in a way that creates susceptibilities to dysfunction for both thyroid and kidney.…”

Section: Discussionmentioning

confidence: 99%

“…Thyroid function: Independent SNPs with minor allele frequency >1% have been identified in GWASs ( p < 5 • 10 -8 ) among Europeans for TSH (N SNPs = 42) and fT4 (N = 21) concentrations in the reference range (42)(43)(44), TPOAb concentration (N = 5) (45,46), and hypothyroidism (N = 30) (39-41) (Supplementary Data). In the study by Pickrell et al using data from 23andMe, Inc., the diagnosis of hypothyroidism was Individuals contributing to these analyses all had European ancestry.…”

Section: Genetic Instrumentsmentioning

confidence: 99%

“…As we tested four primary but related traits by MR (hypothyroidism, TSH, fT4, and TPOAb), we considered a twotailed p-value <0.013 (0.05/4) to be significant (Bonferroni correction). In published GWASs, TSH and fT4 were therefore scaled to study-specific standard deviation (SD) units (42,43). Traits in the WGHS were scaled using the WGHS SDs.…”

Section: Statisticsmentioning

confidence: 99%

“…We used bidirectional MR to assess the mechanisms and direction of effects between thyroid and kidney functions. We selected single-nucleotide polymorphism (SNP) GWAS instruments to address various measures of thyroid function, namely hypothyroidism (39)(40)(41), increased TSH within the reference range (42)(43)(44), increased fT4 within the reference range (42)(43)(44), and increased antibodies against thyroid peroxidase (TPOAb) (45,46), to predict kidney function [estimated glomerular filtration rate from creatinine [eGFR crea ] (47), eGFR from cystatin C [eGFR cys ] (48), CKD (47), and UACR (49)] in the Women's Genome Health Study (WGHS) and through published GWAS summary statistics from the Chronic Kidney Disease Genetics Consortium (CKDGen). In addition, in the WGHS, we used GWAS-identified SNP instruments for kidney function as predictors of thyroid function, and thereby investigate reverse directionality.…”

Section: Introductionmentioning

confidence: 99%

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Hypothyroidism and Kidney Function: A Mendelian Randomization Study

Ellervik

Mora

Ridker

et al. 2020

Thyroid

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Background: Uncertainty in the mechanism and directionality of observational associations between thyroid function and kidney function may be addressed by genetic analysis with an instrumental variable method termed bidirectional Mendelian randomization (MR). Methods: In the Women's Genome Health Study (WGHS), observational associations between thyroid measures and kidney function were evaluated. Genetic instruments for MR were from recent genome-wide association studies (GWAS) of hypothyroidism, thyrotropin (TSH), and free thyroxine (fT4) concentrations within the reference range, thyroid peroxidase antibodies (TPOAb), estimated glomerular filtration rate from creatinine (eGFR crea ), eGFR from cystatin C (eGFR cys ), and chronic kidney disease (CKD). In WGHS individual-level data, these instruments were used for bidirectional MR between thyroid (N = 3336) and kidney (N = 23,186) functions. To increase power, MR was also performed using GWAS summary statistics from the Chronic Kidney Disease Genetics Consortium (CKDGen) for eGFR crea (N = 567,460), eGFR cys (N = 24,063), CKD [N(total) = 480,698, N(cases) = 41,395], and urinary albumin/creatinine ratio (UACR/N = 54,450). Results: In the WGHS, hypothyroidism was observationally associated with decreased eGFR crea [beta (standard error, SE): -0.024 (0.009) ln(mL/min/1.73 m 2 ), p = 0.01]. By MR, hypothyroidism was associated with decreased eGFR crea in the WGHS [beta (SE): -0.007 (0.002) per doubled odds hypothyroidism, p = 1.7 • 10 -3 ] and in CKDGen [beta (SE): -0.004 (0.0005), p = 2.0 • 10 -22 ], and robust to sensitivity analysis. Hypothyroidism was also associated by MR with increased CKD in CKDGen (odds ratio, OR [confidence interval,

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Section: Discussionmentioning

confidence: 99%

Section: Genetic Instrumentsmentioning

confidence: 99%

Section: Statisticsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hypothyroidism and Kidney Function: A Mendelian Randomization Study

Ellervik

Mora

Ridker

et al. 2020

Thyroid

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“…The first GWAS on TSH levels amongst 4300 participants in Sardinia identified one GWS locus rs4704397 (p = 1.3 × 10 −11 ) [89]. Since then, several GWAS have revealed a total of 109 significant independent genetic associations with thyroid traits of TSH, fT4, hypothyroidism and hyperthyroidism [90][91][92][93]. The most recent TSH GWAS meta-analysis of these previous and new GWAS datasets comprised a total of 119,715 individuals and identified 28 new loci, bringing the total number of TSH associated loci to 74 [93].…”

Section: G Enome-wide a Ssociation S Tudie Smentioning

confidence: 99%

Migraine and thyroid dysfunction: Co‐occurrence, shared genes and biological mechanisms

Tasnim

Nyholt

2023

Euro J of Neurology

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Background and purpose: Migraine and thyroid dysfunction, particularly hypothyroidism, are common medical conditions and are known to have high heritability. Thyroid function measures, thyroid stimulating hormone (TSH) and free thyroxine (fT4), are also known to be genetically influenced. Although observational epidemiological studies report an increased co-occurrence of migraine and thyroid dysfunction, a clear and combined interpretation of the findings is currently lacking. A narrative review is provided of the epidemiological and genetic association evidence linking migraine, hypothyroidism, hyperthyroidism and thyroid hormones TSH and fT4.Methods: An extensive literature search was conducted in the PubMed database for epidemiological, candidate gene and genome-wide association studies using the terms migraine, headache, thyroid hormones, TSH, fT4, thyroid function, hypothyroidism and hyperthyroidism.Results: Epidemiological studies suggest a bidirectional relationship between migraine and thyroid dysfunction. However, the nature of the relationship remains unclear, with some studies suggesting migraine increases the risk for thyroid dysfunction whilst other studies suggest the reverse. Early candidate gene studies have provided nominal evidence for MTHFR and APOE, whilst more recently genome-wide association studies have provided robust evidence for THADA and ITPK1 being associated with both migraine and thyroid dysfunction.Conclusions: These genetic associations improve our understanding of the genetic relationship between migraine and thyroid dysfunction, provide an opportunity to develop biomarkers to identify migraine patients most likely to benefit from thyroid hormone therapy, and indicate that further cross-trait genetic studies have excellent potential to provide biological insight into their relationship and inform clinical interventions.

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Thyroid‐associated genetic polymorphisms in relation to breast cancer risk in the Malmö Diet and Cancer Study

Brandt

Borgquist

Almgren

et al. 2017

Intl Journal of Cancer

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Previous studies have suggested that thyroid function is associated with breast cancer risk, which could have an important clinical impact, as one in eight women will develop a thyroid disorder during her lifetime. However, the underlying pathomechanism behind the association is still unknown. We used the Malmö Diet and Cancer Study (a population-based prospective study consisting of 17,035 women) to examine 17 single nucleotide polymorphisms (SNPs) previously related to levels of free thyroxine (free T4) and thyroid peroxidase antibodies (TPO-Ab) as potential genetic risk factors for breast cancer. A baseline examination including free T4 and TPO-Ab levels was conducted at the time of inclusion. Genotyping was performed on 901 breast cancer patients and 3335 controls. Odds ratios (95% confidence intervals) for high free T4, TPO-Ab positivity, and breast cancer were calculated by logistic regression and adjusted for confounders. We identified one free T4-related SNP (rs2235544, D101 gene) that was significantly associated with both free T4 level and breast cancer risk. There was a suggested association between rs11675434 (TPO gene) and TPO-Ab level, and TPO-Ab-related rs11675434 (TPO), rs3094228 (HCP5), rs1033662 (no registered gene), and rs301806 (RERE) were associated with breast cancer risk. There was an indicated interaction between rs6485050 (no registered gene) and free T4 level in regards to breast cancer risk. This is the first study to suggest an association between thyroid-related SNPs and breast cancer risk. All SNPs have a biological plausibility of being associated with breast cancer risk, and may contribute to the genetic predisposition to breast cancer.

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Erratum: Whole-genome sequence-based analysis of thyroid function

Cited by 13 publications

References 0 publications

Hypothyroidism and Kidney Function: A Mendelian Randomization Study

Hypothyroidism and Kidney Function: A Mendelian Randomization Study

Migraine and thyroid dysfunction: Co‐occurrence, shared genes and biological mechanisms

Thyroid‐associated genetic polymorphisms in relation to breast cancer risk in the Malmö Diet and Cancer Study

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