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Genetic Architecture of Complex Traits

Building upon a foundation of quantitative genetics laid over a century ago, applying modern genomic approaches to resolve how genetic and non-genetic factors shape variation in human diseases and traits.

Overview

A major goal of human genetics is to decompose the sources of trait variation into constituent causal factors. The hope is to better understand both the evolutionary forces that have shaped the number, frequency, and interactions of alleles influencing traits, and to identify potential levers of intervention to better predict or influence those traits. Although the foundation of quantitative genetics was laid over a century ago, there continue to be disagreements, both philosophical and empirical, about how to identify and interpret the interplay of genetic and non-genetic factors on trait variation. These issues have recently risen to the fore as large-scale genome-wide association studies (GWAS) reveal differences in apparent genetic effects across families and populations with increasing interest in identifying the sources of that heterogeneity. It is now clear that association studies may be confounded by interdependencies across scales of biological, social, and ecological organization that limit the interpretation and application of genetic findings, especially for the most complex human traits. Fortunately, the growing availability of large-scale human genetic, genomic, and phenotypic data affords opportunities to revisit our existing models and frameworks, develop new approaches, and leverage complexity to improve our understanding of phenotypic variation in people. 

Goals

To support research into the genetic architecture of complex human traits through investigator-initiated projects, coordinated research efforts, and informational outreach activities.  

Events and Meetings

Webinar Series: Complex Trait Genetics

Following on the heels of NHGRI’s workshop “Advances in the Genetic Architecture of Complex Human Traits” is a seminar series picking up where the workshop left off to further explore recent progress and outstanding challenges for delineating and understanding human complex trait genetics.

October 23, 2024    12:00 - 1:00 PM 

Webinar: Ancient Genetic Clues into Modern Human Disease

Traditionally used to elucidate human evolutionary history, ancient DNA (aDNA) is now being applied towards illuminating contemporary human diseases and traits. This webinar will seek input from the research community on how to build ethical and equitable resources of aDNA that represent the genetic diversity of human populations across space and time. Addressing this diversity may mitigate future disparities as aDNA is increasingly used to discern why certain diseases and traits vary across places and populations. 

October 15, 2024    10:00 AM - 12:00 PM

Workshop: Advances in the Genetic Architecture of Complex Human Traits

An historically grounded and forward-looking assessment of the genetic architecture of complex traits in humans. The workshop surveyed the current state of the field, identified gaps and emerging opportunities, and explored future research directions in the genetics of complex traits, from cells and tissues to individuals and populations. 

November 16-17, 2023 

Funding Opportunities

Developing Novel Theory and Methods for Understanding the Genetic Architecture of Complex Human Traits (R01 Clinical Trial Not Allowed) 
PAR-25-255
Application Due Dates: Standard Dates 
Expiration Date: November 6, 2026
  

Developing Novel Theory and Methods for Understanding the Genetic Architecture of Complex Human Traits (R21 Clinical Trial Not Allowed) 
PAR-25-256
Application Due Dates: Standard Dates 
Expiration Date: January 8, 2027 

Program Staff

Alexander Arguello
Alexander Arguello, Ph.D.
  • Program Director
  • Division of Genome Sciences
Ismail Safi
Ismail Safi, Pharm.D.
  • Program Specialist
  • Division of Genome Sciences

Last updated: December 4, 2024