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Article ; Online: Shared genomic segment analysis with equivalence testing.

Horpaopan, Sukanya / Fann, Cathy S J / Lathrop, Mark / Ott, Jurg

2020 Volume 44, Issue 7, Page(s) 741–747

Abstract: An important aspect of disease gene mapping is replication, that is, a putative finding in one group of individuals is confirmed in another set of individuals. As it can happen by chance that individuals share an estimated disease position, we developed ... ...

Abstract	An important aspect of disease gene mapping is replication, that is, a putative finding in one group of individuals is confirmed in another set of individuals. As it can happen by chance that individuals share an estimated disease position, we developed a statistical approach to determine the p-value for multiple individuals or families to share a possibly small number of candidate susceptibility variants. Here, we focus on candidate variants for dominant traits that have been obtained by our previously developed heterozygosity analysis, and we are testing the sharing of candidate variants obtained for different individuals. Our approach allows for multiple pathogenic variants in a gene to contribute to disease, and for estimated disease variant positions to be imprecise. Statistically, the method developed here falls into the category of equivalence testing, where the classical null and alternative hypotheses of homogeneity and heterogeneity are reversed. The null hypothesis situation is created by permuting genomic locations of variants for one individual after another. We applied our methodology to the ALSPAC data set of 1,927 whole-genome sequenced individuals, where some individuals carry a pathogenic variant for the BRCA1 gene, but no two individuals carry the same variant. Our shared genomic segment analysis found significant evidence for BRCA1 pathogenic variants within ±5 kb of a given DNA variant.
MeSH term(s)	BRCA1 Protein/genetics ; Chromosome Mapping/methods ; Genes, BRCA1 ; Genetic Predisposition to Disease/genetics ; Genetics, Population/methods ; Genomics/methods ; Heterozygote ; Humans ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Whole Genome Sequencing/methods
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human
Language	English
Publishing date	2020-07-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605785-8
ISSN	1098-2272 ; 0741-0395
ISSN (online)	1098-2272
ISSN	0741-0395
DOI	10.1002/gepi.22335
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Article ; Online: Precision medicine from the renal cancer genome.

Riazalhosseini, Yasser / Lathrop, Mark

Nature reviews. Nephrology

2016 Volume 12, Issue 11, Page(s) 655–666

Abstract: Genomics is revolutionizing our understanding of the molecular basis of renal cell carcinoma (RCC). The advent of unbiased genome-wide association studies has led to the discovery of previously unrecognized genetic predisposing factors that impact an ... ...

Abstract	Genomics is revolutionizing our understanding of the molecular basis of renal cell carcinoma (RCC). The advent of unbiased genome-wide association studies has led to the discovery of previously unrecognized genetic predisposing factors that impact an individual's risk of developing RCC. Moreover, large-scale investigations of somatic alterations of the genomic and transcriptomic landscapes in tumours using next-generation sequencing technology have revealed new information on the molecular pathways that are characteristically disrupted in various RCC subtypes. Sequencing studies have revealed that epigenetic machinery and chromatin remodelling complexes are disrupted in >80% of clear cell RCC tumours, the most common form of the disease. The growing knowledge of subtype-specific molecular abnormalities arising from genomics has opened new avenues towards the development of molecular diagnostics for RCC subtypes, and for the rational design of therapeutic approaches tailored to patients based on the molecular profiles of their tumours. Genomic studies have also pinpointed a possible role of environmental exposure to aristolochic acid, a nephrotoxin, in the genesis of the disease in some regions of central Europe. In this Review, we discuss the impact of genomics in identifying the genes and environmental exposures involved in disease susceptibility, and in discovering the molecular pathways that are disrupted somatically in different RCC subtypes. Further, we explore the possibilities provided by this genomic knowledge in providing a precision medicine approach for diagnosing and treating RCC.
MeSH term(s)	Carcinoma, Renal Cell/diagnosis ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/therapy ; Genome ; Humans ; Kidney Neoplasms/diagnosis ; Kidney Neoplasms/genetics ; Kidney Neoplasms/therapy ; Mutation ; Precision Medicine
Language	English
Publishing date	2016-11
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2490366-8
ISSN	1759-507X ; 1759-5061
ISSN (online)	1759-507X
ISSN	1759-5061
DOI	10.1038/nrneph.2016.133
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Article ; Online: Differentially methylated CpGs in response to growth hormone administration in children with idiopathic short stature.

Shao, Xiaojian / Le Stunff, Catherine / Cheung, Warren / Kwan, Tony / Lathrop, Mark / Pastinen, Tomi / Bougnères, Pierre

Clinical epigenetics

2022 Volume 14, Issue 1, Page(s) 65

Abstract: Background: Recombinant human growth hormone (rhGH) has shown a great growth-promoting potential in children with idiopathic short stature (ISS). However, the response to rhGH differs across individuals, largely due to genetic and epigenetic ... ...

Abstract	Background: Recombinant human growth hormone (rhGH) has shown a great growth-promoting potential in children with idiopathic short stature (ISS). However, the response to rhGH differs across individuals, largely due to genetic and epigenetic heterogeneity. Since epigenetic marks on the methylome can be dynamically influenced by GH, we performed a comprehensive pharmacoepigenomics analysis of DNA methylation changes associated with long-term rhGH administration in children with ISS. Results: We measured DNA methylation profiles before and after GH treatment (with a duration of ~ 18 months in average) on 47 healthy children using customized methylC-seq capture sequencing. Their changes were compared and associated with changes in plasma IGF1 by adjusting sex, age, treatment duration and estimated blood proportions. We observed a considerable inter-individual heterogeneity of DNA methylation changes responding to GH treatment. We identified 267 response-associated differentially methylated cytosines (DMCs) that were enriched in promoter regions, CpG islands and blood cell-type-specific regulatory elements. Furthermore, the genes associated with these DMCs were enriched in the biology process of "cell development," "neuron differentiation" and "developmental growth," and in the TGF-beta signaling pathway, PPAR Alpha pathway, endoderm differentiation pathway, adipocytokine signaling pathway as well as PI3K-Akt signaling pathway, and cAMP signaling pathway. Conclusion: Our study provides a first insight in DNA methylation changes associated with rhGH administration, which may help understand mechanisms of epigenetic regulation on GH-responsive genes.
MeSH term(s)	Child ; CpG Islands ; DNA Methylation ; Epigenesis, Genetic ; Growth Disorders/blood ; Growth Disorders/drug therapy ; Human Growth Hormone/administration & dosage ; Humans ; Insulin-Like Growth Factor I/metabolism ; Phosphatidylinositol 3-Kinases ; Recombinant Proteins
Chemical Substances	IGF1 protein, human ; Recombinant Proteins ; Human Growth Hormone (12629-01-5) ; Insulin-Like Growth Factor I (67763-96-6)
Language	English
Publishing date	2022-05-18
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-022-01281-z
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Article ; Online: Contribution of genetic variants in the development of familial premature coronary artery disease in a cohort of cardiac patients.

Clinical genetics

2024 Volume 105, Issue 6, Page(s) 611–619

Abstract: Coronary artery disease (CAD), the most prevalent cardiovascular disease, is the leading cause of death worldwide. Heritable factors play a significant role in the pathogenesis of CAD. It has been proposed that approximately one-third of patients with ... ...

Abstract	Coronary artery disease (CAD), the most prevalent cardiovascular disease, is the leading cause of death worldwide. Heritable factors play a significant role in the pathogenesis of CAD. It has been proposed that approximately one-third of patients with CAD have a positive family history, and individuals with such history are at ~1.5-fold increased risk of CAD in their lifespans. Accordingly, the long-recognized familial clustering of CAD is a strong risk factor for this disease. Our study aimed to identify candidate genetic variants contributing to CAD by studying a cohort of 60 large Iranian families with at least two members in different generations afflicted with premature CAD (PCAD), defined as established disease at ≤45 years in men and ≤55 years in women. Exome sequencing was performed for a subset of the affected individuals, followed by prioritization and Sanger sequencing of candidate variants in all available family members. Subsequently, apparently healthy carriers of potential risk variants underwent coronary computed tomography angiography (CCTA), followed by co-segregation analysis of the combined data. Putative causal variants were identified in seven genes, ABCG8, CD36, CYP27A1, PIK3C2G, RASSF9, RYR2, and ZFYVE21, co-segregating with familial PCAD in seven unrelated families. Among these, PIK3C2G, RASSF9, and ZFYVE21 are novel candidate CAD susceptibility genes. Our findings indicate that rare variants in genes identified in this study are involved in CAD development.
MeSH term(s)	Humans ; Coronary Artery Disease/genetics ; Coronary Artery Disease/epidemiology ; Female ; Male ; Genetic Predisposition to Disease ; Middle Aged ; Adult ; Pedigree ; Genetic Variation ; Cohort Studies ; Exome Sequencing ; Iran/epidemiology ; Risk Factors
Language	English
Publishing date	2024-02-03
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	221209-2
ISSN	1399-0004 ; 0009-9163
ISSN (online)	1399-0004
ISSN	0009-9163
DOI	10.1111/cge.14491
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Article ; Online: Genomic regulation of type 2 diabetes endophenotypes: Contribution from genetic studies in the Goto-Kakizaki rat.

Bihoreau, Marie-Thérèse / Dumas, Marc-Emmanuel / Lathrop, Mark / Gauguier, Dominique

Biochimie

2017 Volume 143, Page(s) 56–65

Abstract: The inbred Goto-Kakizaki (GK) rat strain is a unique model of spontaneous type 2 diabetes mellitus caused by naturally occurring genetic variants that have been selectively isolated from an outbred colony of Wistar rats. Genetic and genomic studies in ... ...

Abstract	The inbred Goto-Kakizaki (GK) rat strain is a unique model of spontaneous type 2 diabetes mellitus caused by naturally occurring genetic variants that have been selectively isolated from an outbred colony of Wistar rats. Genetic and genomic studies in experimental crosses and congenic strains of the GK have shed light on the complex etiopathogenesis of diabetes phenotypes in this model. Diabetes-related phenotypes in the GK are under polygenic control and distinct genetic loci regulate glucose tolerance, insulin secretion, β-cell mass and plasma lipids. Metabolome and transcriptome profiling data in GK crosses and congenics, combined with GK genome resequencing, have resulted in a comprehensive landscape of genomic regulations of metabolism that can disentangle causal relationships between GK variants and diabetes phenotypes. Application of systems biology and systems genetics in the GK has contributed to improve our understanding of the fundamental mechanisms regulating metabolism. The wealth of physiological, genetic and genomic information in this strain makes it one of the most powerful model systems to improve our understanding of genetic regulations of metabolism and for testing therapeutic solutions for diabetes.
MeSH term(s)	Animals ; Chromosome Mapping ; Diabetes Mellitus, Experimental/genetics ; Diabetes Mellitus, Type 2/etiology ; Diabetes Mellitus, Type 2/genetics ; Gene Expression Regulation ; Phenotype ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Rats, Inbred Strains ; Rats, Wistar
Language	English
Publishing date	2017-08-24
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2017.08.012
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Article ; Online: A tool for RNA sequencing sample identity check.

Huang, Jinyan / Chen, Jun / Lathrop, Mark / Liang, Liming

Bioinformatics (Oxford, England)

2013 Volume 29, Issue 11, Page(s) 1463–1464

Abstract: Summary: RNA sequencing data are becoming a major method of choice to study transcriptomes, including the mapping of gene expression quantitative trait loci (eQTLs). RNA sample contamination or swapping is a serious problem for downstream analysis and ... ...

Abstract	Summary: RNA sequencing data are becoming a major method of choice to study transcriptomes, including the mapping of gene expression quantitative trait loci (eQTLs). RNA sample contamination or swapping is a serious problem for downstream analysis and may result in false discovery and lose power to detect the true biological relationships. When genetic data are available, for example, in eQTL studies or samples have been previously genotyped or DNA sequenced, it is possible to combine genetic data and RNA-seq data to detect sample contamination and resolve sample swapping problems. In this article, we introduce a tool (IDCheck) that allows easy assessment of concordance between genotype (from SNP arrays or DNA sequencing) and gene expression (RNA-seq) samples. IDCheck compares the identity of RNA-seq reads and SNP genotypes using a likelihood-based method. Based on maximum likelihood estimates of relevant parameters, we can detect sample contamination and identify correct sample pairs when swapping occurs. Our tool provides an efficient and convenient way to evaluate and resolve these problems. Availability: A complete description of the software is included on the application home page. The software is freely available in the public domain at http://eqtl.rc.fas.harvard.edu/idcheck/. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Gene Expression Profiling ; Genotype ; Likelihood Functions ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Sequence Analysis, RNA/methods ; Software
Language	English
Publishing date	2013-06-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btt155
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Article ; Online: Cohort profile: genomic data for 26 622 individuals from the Canadian Longitudinal Study on Aging (CLSA).

Forgetta, Vincenzo / Li, Rui / Darmond-Zwaig, Corinne / Belisle, Alexandre / Balion, Cynthia / Roshandel, Delnaz / Wolfson, Christina / Lettre, Guillaume / Pare, Guillaume / Paterson, Andrew D / Griffith, Lauren E / Verschoor, Chris / Lathrop, Mark / Kirkland, Susan / Raina, Parminder / Richards, J Brent / Ragoussis, Jiannis

BMJ open

2022 Volume 12, Issue 3, Page(s) e059021

Abstract: Purpose: The Canadian Longitudinal Study on Aging (CLSA) Comprehensive cohort was established to provide unique opportunities to study the genetic and environmental contributions to human disease as well as ageing process. The aim of this report was to ... ...

Abstract	Purpose: The Canadian Longitudinal Study on Aging (CLSA) Comprehensive cohort was established to provide unique opportunities to study the genetic and environmental contributions to human disease as well as ageing process. The aim of this report was to describe the genomic data included in CLSA. Participants: A total of 26 622 individuals from the CLSA Comprehensive cohort of men and women aged 45-85 recruited between 2010 and 2015 underwent genome-wide genotyping of DNA samples collected from blood. Comprehensive quality control metrics were measured for genetic markers and samples, respectively. The genotypes were imputed to the TOPMed reference panel. Sex chromosome abnormalities were identified by copy number profiling. Classical human leukocyte antigen gene haplotypes were imputed at two-field (four-digit). Findings to date: Of the 26 622 genotyped participants, 24 655 (92.6%) were identified as having European ancestry. These genomic data were linked to physical, lifestyle, medical, economic, environmental and psychosocial factors collected longitudinally in CLSA. The combined analysis, including CLSA genomic data, uncovered over 100 novel loci associated with key parameters to define glaucoma. The CLSA genomic dataset validated the contribution of a polygenic risk score to screen individuals with high fracture risk. It is also a valuable resource to directly identify common genetic variations associated with conditions related to complex traits. Taking advantage of the comprehensive interview and physical information collected in CLSA, this genomic dataset has been linked to psychosocial factors to investigate both the independent and interactive effects on cardiovascular disease. Future plans: The CLSA overall is ongoing. Follow-up data will continue to be collected from participants in the current genomic subcohort, including the DNA methylation and metabolomic data. Ongoing studies focus on elucidating the role of genetic factors in cognitive decline and cardiovascular diseases. This genomic data resource is available on request through the CLSA data access application process.
MeSH term(s)	Aging/psychology ; Canada ; Female ; Genomics ; Glaucoma ; Humans ; Longitudinal Studies ; Male
Language	English
Publishing date	2022-03-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2021-059021
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Article ; Online: Using spatio-temporal surveillance data to test the infectious environment of children before type 1 diabetes diagnosis.

Bougnères, Pierre / Le Fur, Sophie / Valtat, Sophie / Kamatani, Yoichiro / Lathrop, Mark / Valleron, Alain-Jacques

PloS one

2017 Volume 12, Issue 2, Page(s) e0170658

Abstract: The "hygiene hypothesis" postulates that reduced exposure to infections favours the development of autoimmunity and childhood type 1 diabetes (T1D). But on the other side, viruses, notably enteroviruses, are suspected to trigger T1D. The assessment of ... ...

Abstract	The "hygiene hypothesis" postulates that reduced exposure to infections favours the development of autoimmunity and childhood type 1 diabetes (T1D). But on the other side, viruses, notably enteroviruses, are suspected to trigger T1D. The assessment of the possible relationships between infections and T1D still defies the classical tools of epidemiology. We report the methods and results of a geographical approach that maps the addresses of patients to a communicable diseases surveillance database. We mapped the addresses of patients at birth, infancy and T1D diagnosis to the weekly estimates of the regional incidences of 5 frequent communicable diseases routinely collected since 1984 by the French Sentinel network. The pre-diagnostic infectious environment of 3548 patients with T1D diagnosed between 0.5 and 15 years was compared to those of 100 series of age-matched "virtual controls" drawn randomly on the map. Associations were classified as "suggestive" (summer diarrhea, SD, and varicella, V) when p< 0.05, or "significant" (influenza-like infections, ILI) when they passed the Bonferroni correction for FDR. Exposure to ILI and SD were associated with T1D risk, while V seemed protective. In the subset of 2521 patients for which we had genome wide data, we used a case-only approach to search for interactions between SNPs and the infectious environment as defined by the Sentinel database. Two SNPs, rs116624278 and rs77232854, showed significant interaction with exposure to V between 1 and 3 years of life. The infectious associations found should be taken as possible markers of patients' environment, not as direct causative factors of T1D. They require replication in other populations. The increasing public availability of geographical environmental databases will expand the present approach to map thousands of environmental factors to the lifeline of patients affected by various diseases.
MeSH term(s)	Adolescent ; Autoimmunity/physiology ; Child ; Child, Preschool ; Communicable Diseases/microbiology ; Communicable Diseases/virology ; Databases, Factual ; Diabetes Mellitus, Type 1/etiology ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/physiopathology ; Environment ; Environmental Exposure ; Female ; France ; Genotype ; Geography ; Humans ; Infant ; Insulin-Secreting Cells/pathology ; Male ; Polymorphism, Single Nucleotide/genetics ; Virus Diseases/pathology
Language	English
Publishing date	2017-02-02
Publishing country	United States
Document type	Journal Article ; Multicenter Study
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0170658
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Article ; Online: Genetic Insights on the Relation of Vascular Risk Factors and Cervical Artery Dissection.

Journal of the American College of Cardiology

2023 Volume 82, Issue 14, Page(s) 1411–1423

Abstract: Background: The association between vascular risk factors and cervical artery dissections (CeADs), a leading cause of ischemic stroke (IS) in the young, remains controversial.: Objectives: This study aimed to explore the causal relation of vascular ... ...

Abstract	Background: The association between vascular risk factors and cervical artery dissections (CeADs), a leading cause of ischemic stroke (IS) in the young, remains controversial. Objectives: This study aimed to explore the causal relation of vascular risk factors with CeAD risk and recurrence and compare it to their relation with non-CeAD IS. Methods: This study used 2-sample Mendelian randomization analyses to explore the association of blood pressure (BP), lipid levels, type 2 diabetes, waist-to-hip ratio, smoking, and body mass index with CeAD and non-CeAD IS. To simulate effects of the most frequently used BP-lowering drugs, this study constructed genetic proxies and tested their association with CeAD and non-CeAD IS. In analyses among patients with CeAD, the investigators studied the association between weighted genetic risk scores of vascular risk factors and the risk of multiple or early recurrent dissections. Results: Genetically determined higher systolic BP (OR: 1.51; 95% CI: 1.32-1.72) and diastolic BP (OR: 2.40; 95% CI: 1.92-3.00) increased the risk of CeAD (P < 0.0001). Genetically determined higher body mass index was inconsistently associated with a lower risk of CeAD. Genetic proxies for β-blocker effects were associated with a lower risk of CeAD (OR: 0.65; 95% CI: 0.50-0.85), whereas calcium-channel blockers were associated with a lower risk of non-CeAD IS (OR: 0.75; 95% CI: 0.63-0.90). Weighted genetic risk scores for systolic BP and diastolic BP were associated with an increased risk of multiple or early recurrent CeAD. Conclusions: These results are supportive of a causal association between higher BP and increased CeAD risk and recurrence and provide genetic evidence for lower CeAD risk under β-blockers. This may inform secondary prevention strategies and trial design for CeAD.
Language	English
Publishing date	2023-09-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	605507-2
ISSN	1558-3597 ; 0735-1097
ISSN (online)	1558-3597
ISSN	0735-1097
DOI	10.1016/j.jacc.2023.07.021
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Zs.A 1846: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Independent risk factors for simvastatin-related myopathy and relevance to different types of muscle symptom.

Hopewell, Jemma C / Offer, Alison / Haynes, Richard / Bowman, Louise / Li, Jing / Chen, Fang / Bulbulia, Richard / Lathrop, Mark / Baigent, Colin / Landray, Martin J / Collins, Rory / Armitage, Jane / Parish, Sarah

European heart journal

2020 Volume 41, Issue 35, Page(s) 3336–3342

Abstract: Aims: Statins are widely used to prevent cardiovascular events, but little is known about the impact of different risk factors for statin-related myopathy or their relevance to reports of other types of muscle symptom.: Methods and results: An ... ...

Abstract	Aims: Statins are widely used to prevent cardiovascular events, but little is known about the impact of different risk factors for statin-related myopathy or their relevance to reports of other types of muscle symptom. Methods and results: An observational analysis was undertaken of 171 clinically adjudicated cases of myopathy (defined as unexplained muscle pain or weakness with creatine kinase >10× upper limit of normal) and, separately, of 15 208 cases of other muscle symptoms among 58 390 individuals with vascular disease treated with simvastatin for a mean of 3.4 years. Cox proportional hazards models were used to identify independent predictors of myopathy. The rate of myopathy was low: 9 per 10 000 person-years of simvastatin therapy. Independent risk factors for myopathy included: simvastatin dose, ethnicity, sex, age, body mass index, medically treated diabetes, concomitant use of niacin-laropiprant, verapamil, beta-blockers, diltiazem and diuretics. In combination, these risk factors predicted more than a 30-fold risk difference between the top and bottom thirds of a myopathy risk score (hazard ratio : 34.35, 95% CI: 12.73-92.69, P across thirds = 9·1 × 10-48). However, despite the strong association with myopathy, this score was not associated with the other reported muscle symptoms (P across thirds = 0.93). Likewise, although SLCO1B1 genotype was associated with myopathy, it was not associated with other muscle symptoms. Conclusions: The absolute risk of simvastatin-related myopathy is low, but individuals at higher risk can be identified to help guide patient management. The lack of association of the myopathy risk score with other muscle symptoms reinforces randomized placebo-controlled evidence that statins do not cause the vast majority of reported muscle symptoms.
MeSH term(s)	Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Liver-Specific Organic Anion Transporter 1 ; Muscles ; Muscular Diseases/chemically induced ; Risk Factors ; Simvastatin/adverse effects
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Liver-Specific Organic Anion Transporter 1 ; SLCO1B1 protein, human ; Simvastatin (AGG2FN16EV)
Language	English
Publishing date	2020-07-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603098-1
ISSN	1522-9645 ; 0195-668X
ISSN (online)	1522-9645
ISSN	0195-668X
DOI	10.1093/eurheartj/ehaa574
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Zs.MO 640: Show issues

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