Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
29039294
TITLE
A Comparison of Heritability Estimates by Classical Twin Modeling and Based on Genome-Wide Genetic Relatedness for Cardiac Conduction Traits.
ABSTRACT
Twin studies have found that ~50% of variance in electrocardiogram (ECG) traits can be explained by genetic factors. However, genetic variants identified through genome-wide association studies explain less than 10% of the total trait variability. Some have argued that the equal environment assumption for the classical twin model might be invalid, resulting in inflated narrow-sense heritability (h 2) estimates, thus explaining part of the 'missing h 2'. Genomic relatedness restricted maximum likelihood (GREML) estimation overcomes this issue. This method uses both family data and genome-wide coverage of common SNPs to determine the degree of relatedness between individuals to estimate both h 2 explained by common SNPs and total h 2. The aim of the current study is to characterize more reliably than previously possible ECG trait h 2 using GREML estimation, and to compare these outcomes to those of the classical twin model. We analyzed ECG traits (heart rate, PR interval, QRS duration, RV5+SV1, QTc interval, Sokolow-Lyon product, and Cornell product) in up to 3,133 twins from the TwinsUK cohort and derived h 2 estimates by both methods. GREML yielded h 2 estimates between 47% and 68%. Classical twin modeling provided similar h 2 estimates, except for the Cornell product, for which the best fit included no genetic factors. We found no evidence that the classical twin model leads to inflated h 2 estimates. Therefore, our study confirms the validity of the equal environment assumption for monozygotic and dizygotic twins and supports the robust basis for future studies exploring genetic variants responsible for the variance of ECG traits.
DATE PUBLISHED
2017 12
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2017/10/19 06:00
medline 2018/07/13 06:00
entrez 2017/10/18 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Nolte IM Nolte Ilja M IM Department of Epidemiology,University of Groningen,University Medical Center Groningen,Groningen,The Netherlands.
Jansweijer JA Jansweijer Joeri A JA Department of Cardiology,University of Amsterdam,Academic Medical Center,Amsterdam,The Netherlands.
Riese H Riese Hariette H Department of Epidemiology,University of Groningen,University Medical Center Groningen,Groningen,The Netherlands.
Asselbergs FW Asselbergs Folkert W FW Department of Cardiology,Division of Heart and Lungs,University Medical Center Utrecht,Utrecht,The Netherlands.
van der Harst P van der Harst Pim P Department of Cardiology,University of Groningen,University Medical Center Groningen,Groningen,The Netherlands.
Spector TD Spector Timothy D TD Department of Twin Research and Genetic Epidemiology,King's College London,London,UK.
Pinto YM Pinto Yigal M YM Department of Cardiology,University of Amsterdam,Academic Medical Center,Amsterdam,The Netherlands.
Snieder H Snieder Harold H Department of Epidemiology,University of Groningen,University Medical Center Groningen,Groningen,The Netherlands.
Jamshidi Y Jamshidi Yalda Y Genetics Unit,Cardiovascular and Cell Sciences Institute,St George's University of London,London,UK.
INVESTIGATORS
JOURNAL
VOLUME: 20
ISSUE: 6
TITLE: Twin research and human genetics : the official journal of the International Society for Twin Studies
ISOABBREVIATION: Twin Res Hum Genet
YEAR: 2017
MONTH: 12
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1832-4274
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Twin Res Hum Genet
COUNTRY: England
ISSNLINKING: 1832-4274
NLMUNIQUEID: 101244624
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
KEYWORD
arrhythmia
genetics
heritability
twin study
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Aged
Cardiac Conduction System Disease physiopathology
Electrocardiography physiopathology
Female physiopathology
Genetic Predisposition to Disease physiopathology
Genome-Wide Association Study physiopathology
Heart Rate genetics
Humans genetics
Male genetics
Middle Aged genetics
Polymorphism, Single Nucleotide genetics
Quantitative Trait Loci genetics
Twins, Dizygotic genetics
Twins, Monozygotic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's