Genetic basis of myocardial infarction: Novel insights from genome-wide association studies

2009 ◽  
Vol 3 (6) ◽  
pp. 426-433 ◽  
Author(s):  
Jeanette Erdmann ◽  
Patrick Linsel-Nitschke ◽  
Heribert Schunkert
Author(s):  
Nasa Sinnott-Armstrong ◽  
Sahin Naqvi ◽  
Manuel Rivas ◽  
Jonathan K Pritchard

SummaryGenome-wide association studies (GWAS) have been used to study the genetic basis of a wide variety of complex diseases and other traits. However, for most traits it remains difficult to interpret what genes and biological processes are impacted by the top hits. Here, as a contrast, we describe UK Biobank GWAS results for three molecular traits—urate, IGF-1, and testosterone—that are biologically simpler than most diseases, and for which we know a great deal in advance about the core genes and pathways. Unlike most GWAS of complex traits, for all three traits we find that most top hits are readily interpretable. We observe huge enrichment of significant signals near genes involved in the relevant biosynthesis, transport, or signaling pathways. We show how GWAS data illuminate the biology of variation in each trait, including insights into differences in testosterone regulation between females and males. Meanwhile, in other respects the results are reminiscent of GWAS for more-complex traits. In particular, even these molecular traits are highly polygenic, with most of the variance coming not from core genes, but from thousands to tens of thousands of variants spread across most of the genome. Given that diseases are often impacted by many distinct biological processes, including these three, our results help to illustrate why so many variants can affect risk for any given disease.


2020 ◽  
Vol 116 (9) ◽  
pp. 1620-1634
Author(s):  
Charlotte Glinge ◽  
Najim Lahrouchi ◽  
Reza Jabbari ◽  
Jacob Tfelt-Hansen ◽  
Connie R Bezzina

Abstract The genetic basis of cardiac electrical phenotypes has in the last 25 years been the subject of intense investigation. While in the first years, such efforts were dominated by the study of familial arrhythmia syndromes, in recent years, large consortia of investigators have successfully pursued genome-wide association studies (GWAS) for the identification of single-nucleotide polymorphisms that govern inter-individual variability in electrocardiographic parameters in the general population. We here provide a review of GWAS conducted on cardiac electrical phenotypes in the last 14 years and discuss the implications of these discoveries for our understanding of the genetic basis of disease susceptibility and variability in disease severity. Furthermore, we review functional follow-up studies that have been conducted on GWAS loci associated with cardiac electrical phenotypes and highlight the challenges and opportunities offered by such studies.


2018 ◽  
Vol 30 (11) ◽  
pp. 2720-2740 ◽  
Author(s):  
Meng Yang ◽  
Kai Lu ◽  
Fang-Jie Zhao ◽  
Weibo Xie ◽  
Priya Ramakrishna ◽  
...  

Plants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1695
Author(s):  
Shuyu Zhao ◽  
Su Jang ◽  
Yoon Kyung Lee ◽  
Dong-Gwan Kim ◽  
Zhengxun Jin ◽  
...  

A tiller number is the key determinant of rice plant architecture and panicle number and consequently controls grain yield. Thus, it is necessary to optimize the tiller number to achieve the maximum yield in rice. However, comprehensive analyses of the genetic basis of the tiller number, considering the development stage, tiller type, and related traits, are lacking. In this study, we sequence 219 Korean rice accessions and construct a high-quality single nucleotide polymorphism (SNP) dataset. We also evaluate the tiller number at different development stages and heading traits involved in phase transitions. By genome-wide association studies (GWASs), we detected 20 significant association signals for all traits. Five signals were detected in genomic regions near known candidate genes. Most of the candidate genes were involved in the phase transition from vegetative to reproductive growth. In particular, HD1 was simultaneously associated with the productive tiller ratio and heading date, indicating that the photoperiodic heading gene directly controls the productive tiller ratio. Multiple linear regression models of lead SNPs showed coefficients of determination (R2) of 0.49, 0.22, and 0.41 for the tiller number at the maximum tillering stage, productive tiller number, and productive tiller ratio, respectively. Furthermore, the model was validated using independent japonica rice collections, implying that the lead SNPs included in the linear regression model were generally applicable to the tiller number prediction. We revealed the genetic basis of the tiller number in rice plants during growth, By GWASs, and formulated a prediction model by linear regression. Our results improve our understanding of tillering in rice plants and provide a basis for breeding high-yield rice varieties with the optimum the tiller number.


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