Faculty Opinions recommendation of Ubiquitous polygenicity of human complex traits: genome-wide analysis of 49 traits in Koreans.

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.

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Genetic impacts on DNA methylation: research findings and future perspectives

Genome Biology ◽

10.1186/s13059-021-02347-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Sergio Villicaña ◽

Jordana T. Bell

Keyword(s):

Dna Methylation ◽

Complex Traits ◽

Genetic Basis ◽

Disease Onset ◽

Significant Proportion ◽

Human Dna ◽

Genome Wide ◽

Research Findings ◽

Methylation Quantitative Trait Loci ◽

Human Complex

AbstractMultiple recent studies highlight that genetic variants can have strong impacts on a significant proportion of the human DNA methylome. Methylation quantitative trait loci, or meQTLs, allow for the exploration of biological mechanisms that underlie complex human phenotypes, with potential insights for human disease onset and progression. In this review, we summarize recent milestones in characterizing the human genetic basis of DNA methylation variation over the last decade, including heritability findings and genome-wide identification of meQTLs. We also discuss challenges in this field and future areas of research geared to generate insights into molecular processes underlying human complex traits.

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Statistical methods to detect pleiotropy in human complex traits

Open Biology ◽

10.1098/rsob.170125 ◽

2017 ◽

Vol 7 (11) ◽

pp. 170125 ◽

Cited By ~ 41

Author(s):

Sophie Hackinger ◽

Eleftheria Zeggini

Keyword(s):

Complex Traits ◽

Genome Wide Association Study ◽

Human Genetics ◽

Genetic Locus ◽

Summary Statistics ◽

Multiple Traits ◽

Future Directions ◽

Genome Wide ◽

Genetic Overlap ◽

Human Complex

In recent years pleiotropy, the phenomenon of one genetic locus influencing several traits, has become a widely researched field in human genetics. With the increasing availability of genome-wide association study summary statistics, as well as the establishment of deeply phenotyped sample collections, it is now possible to systematically assess the genetic overlap between multiple traits and diseases. In addition to increasing power to detect associated variants, multi-trait methods can also aid our understanding of how different disorders are aetiologically linked by highlighting relevant biological pathways. A plethora of available tools to perform such analyses exists, each with their own advantages and limitations. In this review, we outline some of the currently available methods to conduct multi-trait analyses. First, we briefly introduce the concept of pleiotropy and outline the current landscape of pleiotropy research in human genetics; second, we describe analytical considerations and analysis methods; finally, we discuss future directions for the field.

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