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  1. Article: Colocalization of corneal resistance factor GWAS loci with GTEx e/sQTLs highlights plausible candidate causal genes for keratoconus postnatal corneal stroma weakening.

    Jiang, Xinyi / Boutin, Thibaud / Vitart, Veronique

    Frontiers in genetics

    2023  Volume 14, Page(s) 1171217

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2023-08-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2023.1171217
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A mouse model of brittle cornea syndrome caused by mutation in Zfp469.

    Stanton, Chloe M / Findlay, Amy S / Drake, Camilla / Mustafa, Mohammad Z / Gautier, Philippe / McKie, Lisa / Jackson, Ian J / Vitart, Veronique

    Disease models & mechanisms

    2021  Volume 14, Issue 9

    Abstract: Brittle cornea syndrome (BCS) is a rare recessive condition characterised by extreme thinning of the cornea and sclera. BCS results from loss-of-function mutations in the poorly understood genes ZNF469 or PRDM5. In order to determine the function of ... ...

    Abstract Brittle cornea syndrome (BCS) is a rare recessive condition characterised by extreme thinning of the cornea and sclera. BCS results from loss-of-function mutations in the poorly understood genes ZNF469 or PRDM5. In order to determine the function of ZNF469 and to elucidate pathogenic mechanisms, we used genome editing to recapitulate a human ZNF469 BCS mutation in the orthologous mouse gene Zfp469. Ophthalmic phenotyping showed that homozygous Zfp469 mutation causes significant central and peripheral corneal thinning arising from reduced stromal thickness. Expression of key components of the corneal stroma in primary keratocytes from Zfp469BCS/BCS mice is affected, including decreased Col1a1 and Col1a2 expression. This alters the collagen type I/collagen type V ratio and results in collagen fibrils with smaller diameter and increased fibril density in homozygous mutant corneas, correlating with decreased biomechanical strength in the cornea. Cell-derived matrices generated by primary keratocytes show reduced deposition of collagen type I, offering an in vitro model for stromal dysfunction. Work remains to determine whether modulating ZNF469 activity will have therapeutic benefit in BCS or in conditions such as keratoconus in which the cornea thins progressively. This article has an associated First Person interview with the first author of the paper.
    MeSH term(s) Animals ; Cornea ; DNA-Binding Proteins/genetics ; Eye Abnormalities ; Humans ; Joint Instability/congenital ; Mice ; Mutation/genetics ; Skin Abnormalities/genetics ; Transcription Factors/genetics ; Zinc Fingers
    Chemical Substances DNA-Binding Proteins ; PRDM5 protein, mouse ; Transcription Factors
    Language English
    Publishing date 2021-09-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2451104-3
    ISSN 1754-8411 ; 1754-8403
    ISSN (online) 1754-8411
    ISSN 1754-8403
    DOI 10.1242/dmm.049175
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma.

    Hamel, Andrew R / Yan, Wenjun / Rouhana, John M / Monovarfeshani, Aboozar / Jiang, Xinyi / Mehta, Puja A / Advani, Jayshree / Luo, Yuyang / Liang, Qingnan / Rajasundaram, Skanda / Shrivastava, Arushi / Duchinski, Katherine / Mantena, Sreekar / Wang, Jiali / van Zyl, Tavé / Pasquale, Louis R / Swaroop, Anand / Gharahkhani, Puya / Khawaja, Anthony P /
    MacGregor, Stuart / Chen, Rui / Vitart, Veronique / Sanes, Joshua R / Wiggs, Janey L / Segrè, Ayellet V

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 396

    Abstract: Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major ... ...

    Abstract Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP genome-wide association study (GWAS) loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina prioritizes causal genes for 60% of loci. These genes are enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues reveals that the POAG and IOP colocalizing genes and genome-wide associations are enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominates IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis.
    MeSH term(s) Humans ; Genome-Wide Association Study ; Glaucoma, Open-Angle/genetics ; Gene Expression Regulation ; Causality ; Glaucoma/genetics
    Language English
    Publishing date 2024-01-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-44380-y
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  4. Article ; Online: Fine-mapping and cell-specific enrichment at corneal resistance factor loci prioritize candidate causal regulatory variants.

    Jiang, Xinyi / Dellepiane, Nefeli / Pairo-Castineira, Erola / Boutin, Thibaud / Kumar, Yatendra / Bickmore, Wendy A / Vitart, Veronique

    Communications biology

    2020  Volume 3, Issue 1, Page(s) 762

    Abstract: Corneal resistance factor (CRF) is altered during corneal diseases progression. Genome-wide-association studies (GWAS) indicated potential CRF and disease genetics overlap. Here, we characterise 135 CRF loci following GWAS in 76029 UK Biobank ... ...

    Abstract Corneal resistance factor (CRF) is altered during corneal diseases progression. Genome-wide-association studies (GWAS) indicated potential CRF and disease genetics overlap. Here, we characterise 135 CRF loci following GWAS in 76029 UK Biobank participants. Enrichment of extra-cellular matrix gene-sets, genetic correlation with corneal thickness (70% (SE = 5%)), reported keratoconus risk variants at 13 loci, all support relevance to corneal stroma biology. Fine-mapping identifies a subset of 55 highly likely causal variants, 91% of which are non-coding. Genomic features enrichments, using all associated variants, also indicate prominent regulatory causal role. We newly established open chromatin landscapes in two widely-used human cornea immortalised cell lines using ATAC-seq. Variants associated with CRF were significantly enriched in regulatory regions from the corneal stroma-derived cell line and enrichment increases to over 5 fold for variants prioritised by fine-mapping-including at GAS7, SMAD3 and COL6A1 loci. Our analysis generates many hypotheses for future functional validation of aetiological mechanisms.
    MeSH term(s) Alleles ; Chromosome Mapping ; Computational Biology/methods ; Corneal Diseases/etiology ; Corneal Diseases/metabolism ; Corneal Diseases/pathology ; Databases, Genetic ; Female ; Gene Expression Regulation ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Male ; Molecular Sequence Annotation ; Organ Specificity ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; United Kingdom
    Language English
    Publishing date 2020-12-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-020-01497-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A multi-omics study of circulating phospholipid markers of blood pressure.

    Liu, Jun / de Vries, Paul S / Del Greco M, Fabiola / Johansson, Åsa / Schraut, Katharina E / Hayward, Caroline / van Dijk, Ko Willems / Franco, Oscar H / Hicks, Andrew A / Vitart, Veronique / Rudan, Igor / Campbell, Harry / Polašek, Ozren / Pramstaller, Peter P / Wilson, James F / Gyllensten, Ulf / van Duijn, Cornelia M / Dehghan, Abbas / Demirkan, Ayşe

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 574

    Abstract: High-throughput techniques allow us to measure a wide-range of phospholipids which can provide insight into the mechanisms of hypertension. We aimed to conduct an in-depth multi-omics study of various phospholipids with systolic blood pressure (SBP) and ... ...

    Abstract High-throughput techniques allow us to measure a wide-range of phospholipids which can provide insight into the mechanisms of hypertension. We aimed to conduct an in-depth multi-omics study of various phospholipids with systolic blood pressure (SBP) and diastolic blood pressure (DBP). The associations of blood pressure and 151 plasma phospholipids measured by electrospray ionization tandem mass spectrometry were performed by linear regression in five European cohorts (n = 2786 in discovery and n = 1185 in replication). We further explored the blood pressure-related phospholipids in Erasmus Rucphen Family (ERF) study by associating them with multiple cardiometabolic traits (linear regression) and predicting incident hypertension (Cox regression). Mendelian Randomization (MR) and phenome-wide association study (Phewas) were also explored to further investigate these association results. We identified six phosphatidylethanolamines (PE 38:3, PE 38:4, PE 38:6, PE 40:4, PE 40:5 and PE 40:6) and two phosphatidylcholines (PC 32:1 and PC 40:5) which together predicted incident hypertension with an area under the ROC curve (AUC) of 0.61. The identified eight phospholipids are strongly associated with triglycerides, obesity related traits (e.g. waist, waist-hip ratio, total fat percentage, body mass index, lipid-lowering medication, and leptin), diabetes related traits (e.g. glucose, insulin resistance and insulin) and prevalent type 2 diabetes. The genetic determinants of these phospholipids also associated with many lipoproteins, heart rate, pulse rate and blood cell counts. No significant association was identified by bi-directional MR approach. We identified eight blood pressure-related circulating phospholipids that have a predictive value for incident hypertension. Our cross-omics analyses show that phospholipid metabolites in the circulation may yield insight into blood pressure regulation and raise a number of testable hypothesis for future research.
    MeSH term(s) Adult ; Aged ; Biomarkers/blood ; Blood Pressure ; Cardiometabolic Risk Factors ; Cohort Studies ; Computational Biology ; Diastole ; Female ; Humans ; Hypertension/blood ; Male ; Mendelian Randomization Analysis ; Middle Aged ; Phospholipids/blood ; Systole
    Chemical Substances Biomarkers ; Phospholipids
    Language English
    Publishing date 2022-01-12
    Publishing country England
    Document type Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-04446-7
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  6. Article ; Online: Typing myalgic encephalomyelitis by infection at onset: A DecodeME study.

    Bretherick, Andrew D / McGrath, Simon J / Devereux-Cooke, Andy / Leary, Sian / Northwood, Emma / Redshaw, Anna / Stacey, Pippa / Tripp, Claire / Wilson, Jim / Chowdhury, Sonya / Lewis, Isabel / Almelid, Øyvind / Baby, Sumy V / Baker, Tom / Becher, Hannes / Boutin, Thibaud / Clyde, Malgorzata / Garcia, Diana / Ireland, John /
    Kerr, Shona M / McDowall, Ewan / Perry, David / Samms, Gemma L / Vitart, Veronique / Wolfe, Jareth C / Ponting, Chris P

    NIHR open research

    2023  Volume 3, Page(s) 20

    Abstract: Background: People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience core symptoms of post-exertional malaise, unrefreshing sleep, and cognitive impairment. Despite numbering 0.2-0.4% of the population, no laboratory test is ... ...

    Abstract Background: People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience core symptoms of post-exertional malaise, unrefreshing sleep, and cognitive impairment. Despite numbering 0.2-0.4% of the population, no laboratory test is available for their diagnosis, no effective therapy exists for their treatment, and no scientific breakthrough regarding pathogenesis has been made. It remains unknown, despite decades of small-scale studies, whether individuals experience different types of ME/CFS separated by onset-type, sex or age.
    Methods: DecodeME is a large population-based study of ME/CFS that recruited 17,074 participants in the first 3 months following full launch. Detailed questionnaire responses from UK-based participants who all reported being diagnosed with ME/CFS by a health professional provided an unparalleled opportunity to investigate, using logistic regression, whether ME/CFS severity or onset type is significantly associated with sex, age, illness duration, comorbid conditions or symptoms.
    Results: The well-established sex-bias among ME/CFS patients is evident in the initial DecodeME cohort: 83.5% of participants were females. What was not known previously was that females tend to have more comorbidities than males. Moreover, being female, being older and being over 10 years from ME/CFS onset are significantly associated with greater severity. Five different ME/CFS onset types were examined in the self-reported data: those with ME/CFS onset (i) after glandular fever (infectious mononucleosis); (ii) after COVID-19 infection; (iii) after other infections; (iv) without an infection at onset; and, (v) where the occurrence of an infection at or preceding onset is not known. Among other findings, ME/CFS onset with unknown infection status was significantly associated with active fibromyalgia.
    Conclusions: DecodeME participants differ in symptoms, comorbid conditions and/or illness severity when stratified by their sex-at-birth and/or infection around the time of ME/CFS onset.
    Language English
    Publishing date 2023-08-21
    Publishing country England
    Document type Journal Article
    ISSN 2633-4402
    ISSN (online) 2633-4402
    DOI 10.3310/nihropenres.13421.4
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  7. Article: Electronic health record and genome-wide genetic data in Generation Scotland participants.

    Kerr, Shona M / Campbell, Archie / Marten, Jonathan / Vitart, Veronique / McIntosh, Andrew M / Porteous, David J / Hayward, Caroline

    Wellcome open research

    2017  Volume 2, Page(s) 85

    Abstract: This article provides the first detailed demonstration of the research value of the Electronic Health Record (EHR) linked to research data in Generation Scotland Scottish Family Health Study (GS:SFHS) participants, together with how to access this data. ... ...

    Abstract This article provides the first detailed demonstration of the research value of the Electronic Health Record (EHR) linked to research data in Generation Scotland Scottish Family Health Study (GS:SFHS) participants, together with how to access this data. The structured, coded variables in the routine biochemistry, prescribing and morbidity records, in particular, represent highly valuable phenotypic data for a genomics research resource. Access to a wealth of other specialized datasets, including cancer, mental health and maternity inpatient information, is also possible through the same straightforward and transparent application process. The EHR linked dataset is a key component of GS:SFHS, a biobank conceived in 1999 for the purpose of studying the genetics of health areas of current and projected public health importance. Over 24,000 adults were recruited from 2006 to 2011, with broad and enduring written informed consent for biomedical research. Consent was obtained from 23,603 participants for GS:SFHS study data to be linked to their Scottish National Health Service (NHS) records, using their Community Health Index number. This identifying number is used for NHS Scotland procedures (registrations, attendances, samples, prescribing and investigations) and allows healthcare records for individuals to be linked across time and location. Here, we describe the NHS EHR dataset on the sub-cohort of 20,032 GS:SFHS participants with consent and mechanism for record linkage plus extensive genetic data. Together with existing study phenotypes, including family history and environmental exposures, such as smoking, the EHR is a rich resource of real world data that can be used in research to characterise the health trajectory of participants, available at low cost and a high degree of timeliness, matched to DNA, urine and serum samples and genome-wide genetic information.
    Language English
    Publishing date 2017-09-18
    Publishing country England
    Document type Journal Article
    ISSN 2398-502X
    ISSN 2398-502X
    DOI 10.12688/wellcomeopenres.12600.1
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  8. Article ; Online: Insights into the genetic basis of retinal detachment.

    Boutin, Thibaud S / Charteris, David G / Chandra, Aman / Campbell, Susan / Hayward, Caroline / Campbell, Archie / Nandakumar, Priyanka / Hinds, David / Mitry, Danny / Vitart, Veronique

    Human molecular genetics

    2019  Volume 29, Issue 4, Page(s) 689–702

    Abstract: Retinal detachment (RD) is a serious and common condition, but genetic studies to date have been hampered by the small size of the assembled cohorts. In the UK Biobank data set, where RD was ascertained by self-report or hospital records, genetic ... ...

    Abstract Retinal detachment (RD) is a serious and common condition, but genetic studies to date have been hampered by the small size of the assembled cohorts. In the UK Biobank data set, where RD was ascertained by self-report or hospital records, genetic correlations between RD and high myopia or cataract operation were, respectively, 0.46 (SE = 0.08) and 0.44 (SE = 0.07). These correlations are consistent with known epidemiological associations. Through meta-analysis of genome-wide association studies using UK Biobank RD cases (N = 3 977) and two cohorts, each comprising ~1 000 clinically ascertained rhegmatogenous RD patients, we uncovered 11 genome-wide significant association signals. These are near or within ZC3H11B, BMP3, COL22A1, DLG5, PLCE1, EFEMP2, TYR, FAT3, TRIM29, COL2A1 and LOXL1. Replication in the 23andMe data set, where RD is self-reported by participants, firmly establishes six RD risk loci: FAT3, COL22A1, TYR, BMP3, ZC3H11B and PLCE1. Based on the genetic associations with eye traits described to date, the first two specifically impact risk of a RD, whereas the last four point to shared aetiologies with macular condition, myopia and glaucoma. Fine-mapping prioritized the lead common missense variant (TYR S192Y) as causal variant at the TYR locus and a small set of credible causal variants at the FAT3 locus. The larger study size presented here, enabled by resources linked to health records or self-report, provides novel insights into RD aetiology and underlying pathological pathways.
    MeSH term(s) Case-Control Studies ; Cohort Studies ; Genetic Markers ; Genome-Wide Association Study ; Humans ; Meta-Analysis as Topic ; Retinal Detachment/epidemiology ; Retinal Detachment/genetics ; Retinal Detachment/pathology ; Sweden/epidemiology ; United Kingdom/epidemiology
    Chemical Substances Genetic Markers
    Language English
    Publishing date 2019-12-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108742-0
    ISSN 1460-2083 ; 0964-6906
    ISSN (online) 1460-2083
    ISSN 0964-6906
    DOI 10.1093/hmg/ddz294
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  9. Article ; Online: DecodeME: community recruitment for a large genetics study of myalgic encephalomyelitis / chronic fatigue syndrome.

    Devereux-Cooke, Andy / Leary, Sian / McGrath, Simon J / Northwood, Emma / Redshaw, Anna / Shepherd, Charles / Stacey, Pippa / Tripp, Claire / Wilson, Jim / Mar, Margaret / Boobyer, Danielle / Bromiley, Sam / Chowdhury, Sonya / Dransfield, Claire / Almas, Mohammed / Almelid, Øyvind / Buchanan, David / Garcia, Diana / Ireland, John /
    Kerr, Shona M / Lewis, Isabel / McDowall, Ewan / Migdal, Malgorzata / Murray, Phil / Perry, David / Ponting, Chris P / Vitart, Veronique / Wolfe, Jareth C

    BMC neurology

    2022  Volume 22, Issue 1, Page(s) 269

    Abstract: Background: Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a common, long-term condition characterised by post-exertional malaise, often with fatigue that is not significantly relieved by rest. ME/CFS has no confirmed diagnostic test ... ...

    Abstract Background: Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a common, long-term condition characterised by post-exertional malaise, often with fatigue that is not significantly relieved by rest. ME/CFS has no confirmed diagnostic test or effective treatment and we lack knowledge of its causes. Identification of genes and cellular processes whose disruption adds to ME/CFS risk is a necessary first step towards development of effective therapy.
    Methods: Here we describe DecodeME, an ongoing study co-produced by people with lived experience of ME/CFS and scientists. Together we designed the study and obtained funding and are now recruiting up to 25,000 people in the UK with a clinical diagnosis of ME/CFS. Those eligible for the study are at least 16 years old, pass international study criteria, and lack any alternative diagnoses that can result in chronic fatigue. These will include 5,000 people whose ME/CFS diagnosis was a consequence of SARS-CoV-2 infection. Questionnaires are completed online or on paper. Participants' saliva DNA samples are acquired by post, which improves participation by more severely-affected individuals. Digital marketing and social media approaches resulted in 29,000 people with ME/CFS in the UK pre-registering their interest in participating. We will perform a genome-wide association study, comparing participants' genotypes with those from UK Biobank as controls. This should generate hypotheses regarding the genes, mechanisms and cell types contributing to ME/CFS disease aetiology.
    Discussion: The DecodeME study has been reviewed and given a favourable opinion by the North West - Liverpool Central Research Ethics Committee (21/NW/0169). Relevant documents will be available online ( www.decodeme.org.uk ). Genetic data will be disseminated as associated variants and genomic intervals, and as summary statistics. Results will be reported on the DecodeME website and via open access publications.
    MeSH term(s) Adolescent ; COVID-19 ; Fatigue Syndrome, Chronic/genetics ; Genome-Wide Association Study ; Humans ; Longitudinal Studies ; SARS-CoV-2
    Language English
    Publishing date 2022-07-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041347-6
    ISSN 1471-2377 ; 1471-2377
    ISSN (online) 1471-2377
    ISSN 1471-2377
    DOI 10.1186/s12883-022-02763-6
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  10. Article ; Online: An actionable KCNH2 Long QT Syndrome variant detected by sequence and haplotype analysis in a population research cohort.

    Kerr, Shona M / Klaric, Lucija / Halachev, Mihail / Hayward, Caroline / Boutin, Thibaud S / Meynert, Alison M / Semple, Colin A / Tuiskula, Annukka M / Swan, Heikki / Santoyo-Lopez, Javier / Vitart, Veronique / Haley, Chris / Dean, John / Miedzybrodzka, Zosia / Aitman, Timothy J / Wilson, James F

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 10964

    Abstract: The Viking Health Study Shetland is a population-based research cohort of 2,122 volunteer participants with ancestry from the Shetland Isles in northern Scotland. The high kinship and detailed phenotype data support a range of approaches for associating ... ...

    Abstract The Viking Health Study Shetland is a population-based research cohort of 2,122 volunteer participants with ancestry from the Shetland Isles in northern Scotland. The high kinship and detailed phenotype data support a range of approaches for associating rare genetic variants, enriched in this isolate population, with quantitative traits and diseases. As an exemplar, the c.1750G > A; p.Gly584Ser variant within the coding sequence of the KCNH2 gene implicated in Long QT Syndrome (LQTS), which occurred once in 500 whole genome sequences from this population, was investigated. Targeted sequencing of the KCNH2 gene in family members of the initial participant confirmed the presence of the sequence variant and identified two further members of the same family pedigree who shared the variant. Investigation of these three related participants for whom single nucleotide polymorphism (SNP) array genotypes were available allowed a unique shared haplotype of 1.22 Mb to be defined around this locus. Searching across the full cohort for this haplotype uncovered two additional apparently unrelated individuals with no known genealogical connection to the original kindred. All five participants with the defined haplotype were shown to share the rare variant by targeted Sanger sequencing. If this result were verified in a healthcare setting, it would be considered clinically actionable, and has been actioned in relatives ascertained independently through clinical presentation. The General Practitioners of four study participants with the rare variant were alerted to the research findings by letters outlining the phenotype (prolonged electrocardiographic QTc interval). A lack of detectable haplotype sharing between c.1750G > A; p.Gly584Ser chromosomes from previously reported individuals from Finland and those in this study from Shetland suggests that this mutation has arisen more than once in human history. This study showcases the potential value of isolate population-based research resources for genomic medicine. It also illustrates some challenges around communication of actionable findings in research participants in this context.
    MeSH term(s) Aged ; Cohort Studies ; ERG1 Potassium Channel/genetics ; Electrocardiography ; Female ; Haplotypes ; Humans ; Long QT Syndrome/diagnosis ; Long QT Syndrome/genetics ; Male ; Middle Aged ; Pedigree ; Polymorphism, Single Nucleotide ; Scotland
    Chemical Substances ERG1 Potassium Channel ; KCNH2 protein, human
    Language English
    Publishing date 2019-07-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-47436-6
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