SU27A GLOBAL VIEW OF GENETIC ARCHITECTURE AND PLEIOTROPY IN HUMAN COMPLEX TRAITS

2019 ◽  
Vol 29 ◽  
pp. S1282
Author(s):  
Kyoko Watanabe ◽  
Sven Stringer ◽  
Tinca Polderman ◽  
Danielle Posthuma
2014 ◽  
Vol 23 (22) ◽  
pp. 5893-5905 ◽  
Author(s):  
Xu Zhang ◽  
Erika L. Moen ◽  
Cong Liu ◽  
Wenbo Mu ◽  
Eric R. Gamazon ◽  
...  

2019 ◽  
Author(s):  
Anton E. Shikov ◽  
Alexander V. Predeus ◽  
Yury A. Barbitoff

AbstractOver recent decades, genome-wide association studies (GWAS) have dramatically changed the understanding of human genetics. A recent genetic data release by UK Biobank has allowed many researchers worldwide to have comprehensive look into the genetic architecture of thousands of human phenotypes. In this study, we developed a novel statistical framework to assess phenome-wide significance and genetic pleiotropy across the human phenome based on GWAS summary statistics. We demonstrate widespread sharing of genetic architecture components between distinct groups of traits. Apart from known multiple associations inside the MHC locus, we discover high degree of pleiotropy for genes involved in immune system function, apoptosis, hemostasis cascades, as well as lipid and xenobiotic metabolism. We find several notable examples of novel pleiotropic loci (e.g., the MIR2113 microRNA broadly associated with cognition), and provide several possible mechanisms for these association signals. Our results allow for a functional phenome-wide look into the shared components of genetic architecture of human complex traits, and highlight crucial genes and pathways for their development.


2018 ◽  
Vol 50 (5) ◽  
pp. 746-753 ◽  
Author(s):  
Jian Zeng ◽  
Ronald de Vlaming ◽  
Yang Wu ◽  
Matthew R. Robinson ◽  
Luke R. Lloyd-Jones ◽  
...  

2016 ◽  
Vol 283 (1835) ◽  
pp. 20160569 ◽  
Author(s):  
M. E. Goddard ◽  
K. E. Kemper ◽  
I. M. MacLeod ◽  
A. J. Chamberlain ◽  
B. J. Hayes

Complex or quantitative traits are important in medicine, agriculture and evolution, yet, until recently, few of the polymorphisms that cause variation in these traits were known. Genome-wide association studies (GWAS), based on the ability to assay thousands of single nucleotide polymorphisms (SNPs), have revolutionized our understanding of the genetics of complex traits. We advocate the analysis of GWAS data by a statistical method that fits all SNP effects simultaneously, assuming that these effects are drawn from a prior distribution. We illustrate how this method can be used to predict future phenotypes, to map and identify the causal mutations, and to study the genetic architecture of complex traits. The genetic architecture of complex traits is even more complex than previously thought: in almost every trait studied there are thousands of polymorphisms that explain genetic variation. Methods of predicting future phenotypes, collectively known as genomic selection or genomic prediction, have been widely adopted in livestock and crop breeding, leading to increased rates of genetic improvement.


Author(s):  
Valentin Hivert ◽  
Julia Sidorenko ◽  
Florian Rohart ◽  
Michael E. Goddard ◽  
Jian Yang ◽  
...  

Author(s):  
Toshiyuki Sakai ◽  
Akira Abe ◽  
Motoki Shimizu ◽  
Ryohei Terauchi

Abstract Characterizing epistatic gene interactions is fundamental for understanding the genetic architecture of complex traits. However, due to the large number of potential gene combinations, detecting epistatic gene interactions is computationally demanding. A simple, easy-to-perform method for sensitive detection of epistasis is required. Due to their homozygous nature, use of recombinant inbred lines (RILs) excludes the dominance effect of alleles and interactions involving heterozygous genotypes, thereby allowing detection of epistasis in a simple and interpretable model. Here, we present an approach called RIL-StEp (recombinant inbred lines stepwise epistasis detection) to detect epistasis using single nucleotide polymorphisms in the genome. We applied the method to reveal epistasis affecting rice (Oryza sativa) seed hull color and leaf chlorophyll content and successfully identified pairs of genomic regions that presumably control these phenotypes. This method has the potential to improve our understanding of the genetic architecture of various traits of crops and other organisms.


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