scholarly journals Genetic and environmental determinants of diastolic heart function

2021 ◽  
Author(s):  
Marjola Thanaj ◽  
Johanna Mielke ◽  
Kathryn A McGurk ◽  
Wenjia Bai ◽  
Nicoló Savioli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Function ◽  
Genetic Architecture ◽  
Genome Wide Association Study ◽  
Heart Function ◽  
Biomechanical Stress ◽  
Genome Wide ◽  
A Genome ◽  
Genetic And Environmental Factors ◽  
Ventricular Filling

Diastole is the sequence of physiological events that occur in the heart during ventricular filling and principally depends on myocardial relaxation and chamber stiffness. Abnormal diastolic function is related to many cardiovascular disease processes and is predictive of health outcomes, but its genetic architecture is largely unknown. Here, we use machine learning cardiac motion analysis to measure diastolic functional traits in 39,559 participants of UK Biobank and perform a genome-wide association study. We identified 9 significant, independent loci near genes that are associated with maintaining sarcomeric function under biomechanical stress and genes implicated in the development of cardiomyopathy. Age, sex and diabetes were independent predictors of diastolic function and we found a causal relationship between ventricular stiffness and heart failure. Our results provide novel insights into the genetic and environmental factors influencing diastolic function that are relevant for identifying causal relationships and tractable targets in heart failure.

Abstract 16003: Genetic Variation Associated With Favorable Exercise Response in Patients With Systolic Heart Failure: A Hf-action Trial Substudy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sara Coles ◽  
Stephanie Giamberardino ◽  
Carol Haynes ◽  
Ruicong She ◽  
Hongsheng Gui ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Trial ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Systolic Heart Failure ◽  
Genome Wide Association ◽  
Supervised Exercise ◽  
Genome Wide ◽  
A Genome ◽  
Response To Exercise

Background: Exercise has shown benefit in patients with systolic heart failure, including in the clinical trial Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION). There is heterogeneity in who derives benefit from exercise, and the biologic mechanisms of favorable response to exercise in systolic heart failure are not well understood. Hypothesis: Genetic variation is an underlying factor influencing heterogeneity in response to exercise in patients with systolic heart failure. Methods: The HF-ACTION trial randomized individuals with systolic heart failure (left ventricular ejection fraction <35%) to supervised exercise versus usual care. In this study, we performed a genome wide association study (GWAS) in the HF-ACTION biorepository using the Axiom Biobank1 genotyping array (13,403,591 single nucleotide polymorphisms [SNPs] after quality control on directly genotyped and 1000 genomes imputed data), in N=377 study subjects who completed the supervised exercise arm. Using change in peak VO2 as our outcome, we ran within-ancestry GWASes, modeling SNP effects as both additive and dominant, and conducted across-ancestry meta-analysis within each genetic model. Results: Five loci met genome-wide significance in the European ancestry analyses, 5 loci in the African ancestry, and 8 in the meta-analyses. The two most significantly associated loci across both additive and dominant meta-analysis models were rs111577308 located in the histone acetylation for transcription elongator complex 3 gene ( ELP3, p=1.212x10 -9 ) and rs75444785 located in the phosphodiesterase 4D gene ( PDE4D , p=1.565x10 -9 ). ELP3 is responsible for histone modifications related to DNA transcription factor complexes, and PDE4D is involved in cyclic AMP cell signaling. In silico analysis of these loci showed that they are in linkage with regions associated with skeletal muscle and peripheral vascular disease phenotypes. Conclusions: Using a genome-wide association study in a well-phenotyped clinical trial of exercise in systolic heart failure, we found common genetic variants in genes involved in DNA transcription histone modification and cyclic AMP cell signaling that are associated with a more favorable response to exercise.

scholarly journals Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior

Science ◽  
2019 ◽  
Vol 365 (6456) ◽  
pp. eaat7693 ◽  
Author(s):  
Andrea Ganna ◽  
Karin J. H. Verweij ◽  
Michel G. Nivard ◽  
Robert Maier ◽  
Robbee Wedow ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Genetic Architecture ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Same Sex ◽  
Genome Wide ◽  
A Genome ◽  
Number Of Sexual Partners ◽  
Opposite Sex ◽  
Males And Females

Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for specific genes involved have been underpowered. We performed a genome-wide association study (GWAS) on 477,522 individuals, revealing five loci significantly associated with same-sex sexual behavior. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in same-sex sexual behavior, only partially overlapped between males and females, and do not allow meaningful prediction of an individual’s sexual behavior. Comparing these GWAS results with those for the proportion of same-sex to total number of sexual partners among nonheterosexuals suggests that there is no single continuum from opposite-sex to same-sex sexual behavior. Overall, our findings provide insights into the genetics underlying same-sex sexual behavior and underscore the complexity of sexuality.

scholarly journals Expanding the Genetic Architecture of Nicotine Dependence and its Shared Genetics with Multiple Traits: Findings from the Nicotine Dependence GenOmics (iNDiGO) Consortium

2020 ◽  
Author(s):  
Bryan C. Quach ◽  
Michael J. Bray ◽  
Nathan C. Gaddis ◽  
Mengzhen Liu ◽  
Teemu Palviainen ◽  
...  
Keyword(s):  
Nicotine Dependence ◽  
Genetic Architecture ◽  
Genome Wide Association Study ◽  
African Ancestry ◽  
Multiple Traits ◽  
Expression Of Genes ◽  
Genome Wide ◽  
A Genome ◽  
The Uk ◽  
Smoking Index

AbstractCigarette smoking is the leading cause of preventable morbidity and mortality. Knowledge is evolving on genetics underlying initiation, regular smoking, nicotine dependence (ND), and cessation. We performed a genome-wide association study using the Fagerström Test for ND (FTND) in 58,000 smokers of European or African ancestry. Five genome-wide significant loci, including two novel loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416) were identified, and loci reported for other smoking traits were extended to ND. Using the heaviness of smoking index (HSI) in the UK Biobank (N=33,791), rs2714700 was consistently associated, but rs1862416 was not associated, likely reflecting ND features not captured by the HSI. Both variants were cis-eQTLs (rs2714700 for MAGI2-AS3 in hippocampus, rs1862416 for TENM2 in lung), and expression of genes spanning ND-associated variants was enriched in cerebellum. SNP-based heritability of ND was 8.6%, and ND was genetically correlated with 17 other smoking traits (rg=0.40–0.95) and co-morbidities. Our results emphasize the FTND as a composite phenotype that expands genetic knowledge of smoking, including loci specific to ND.

scholarly journals Elucidating the Genetic Architecture of Fiber Quality in Hemp (Cannabis sativa L.) Using a Genome-Wide Association Study

2020 ◽  
Vol 11 ◽  
Author(s):  
Jordi Petit ◽  
Elma M. J. Salentijn ◽  
Maria-João Paulo ◽  
Christel Denneboom ◽  
Eibertus N. van Loo ◽  
...  
Keyword(s):  
Association Study ◽  
Genetic Architecture ◽  
Genome Wide Association Study ◽  
Cannabis Sativa ◽  
Fiber Quality ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Quantitative interactions: the disease outcome of Botrytis cinerea across the plant kingdom

2021 ◽  
Author(s):  
Celine Caseys ◽  
Gongjun Shi ◽  
Nicole Soltis ◽  
Raoni Gwinner ◽  
Jason Corwin ◽  
...  
Keyword(s):  
Botrytis Cinerea ◽  
Host Specificity ◽  
Genetic Architecture ◽  
Genome Wide Association Study ◽  
Disease Outcome ◽  
Plant Kingdom ◽  
Pathogen Virulence ◽  
Genome Wide ◽  
A Genome ◽  
Functionally Diverse

Abstract Botrytis cinerea is a fungal pathogen that causes necrotic disease on more than a thousand known hosts widely spread across the plant kingdom. How B. cinerea interacts with such extensive host diversity remains largely unknown. To address this question, we generated an infectivity matrix of 98 strains of B. cinerea on 90 genotypes representing eight host plants. This experimental infectivity matrix revealed that the disease outcome is largely explained by variations in either the host resistance or pathogen virulence. However, the specific interactions between host and pathogen account for 16% of the disease outcome. Furthermore, the disease outcomes cluster among genotypes of a species but are independent of the relatedness between hosts. When analyzing the host specificity and virulence of B. cinerea, generalist strains are predominant. In this fungal necrotroph, specialization may happen by a loss in virulence on most hosts rather than an increase of virulence on a specific host. To uncover the genetic architecture of Botrytis host specificity and virulence, a genome-wide association study (GWAS) was performed and revealed up to 1492 genes of interest. The genetic architecture of these traits is widespread across B. cinerea genome. The complexity of the disease outcome might be explained by hundreds of functionally diverse genes putatively involved in adjusting the infection to diverse hosts.

scholarly journals Genome-wide association study identifies 16 genomic regions associated with circulating cytokines at birth

PLoS Genetics ◽  
2020 ◽  
Vol 16 (11) ◽  
pp. e1009163
Author(s):  
Yunpeng Wang ◽  
Ron Nudel ◽  
Michael E. Benros ◽  
Kristin Skogstrand ◽  
Simon Fishilevich ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Inflammatory Markers ◽  
Genetic Architecture ◽  
Complex Disease ◽  
Genome Wide Association Study ◽  
Adult Life ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions ◽  
Circulating Inflammatory Markers

Circulating inflammatory markers are essential to human health and disease, and they are often dysregulated or malfunctioning in cancers as well as in cardiovascular, metabolic, immunologic and neuropsychiatric disorders. However, the genetic contribution to the physiological variation of levels of circulating inflammatory markers is largely unknown. Here we report the results of a genome-wide genetic study of blood concentration of ten cytokines, including the hitherto unexplored calcium-binding protein (S100B). The study leverages a unique sample of neonatal blood spots from 9,459 Danish subjects from the iPSYCH initiative. We estimate the SNP-heritability of marker levels as ranging from essentially zero for Erythropoietin (EPO) up to 73% for S100B. We identify and replicate 16 associated genomic regions (p < 5 x 10−9), of which four are novel. We show that the associated variants map to enhancer elements, suggesting a possible transcriptional effect of genomic variants on the cytokine levels. The identification of the genetic architecture underlying the basic levels of cytokines is likely to prompt studies investigating the relationship between cytokines and complex disease. Our results also suggest that the genetic architecture of cytokines is stable from neonatal to adult life.

Sign in / Sign up

Export Citation Format

Share Document