Format

Send to

Choose Destination
Nat Rev Genet. 2018 Feb;19(2):110-124. doi: 10.1038/nrg.2017.101. Epub 2017 Dec 11.

Genetic architecture: the shape of the genetic contribution to human traits and disease.

Author information

1
MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Clifton, Bristol BS8 2BN, UK.
2
Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, 3755 Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada.
3
Department of Oncology, McGill University, 3755 Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada.
4
Departments of Human Genetics and Epidemiology, Biostatistics and Occupational Health, McGill University, 3755 Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada.
5
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.
6
Department of Haematology, University of Cambridge, Long Road, Cambridge CB2 0PT, UK.
7
Department of Medicine, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, 3755 Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada.
8
Department of Twin Research & Genetic Epidemiology, King's College London, St Thomas' Campus, Lambeth Palace Road, London SE1 7EH, UK.

Abstract

Genetic architecture describes the characteristics of genetic variation that are responsible for heritable phenotypic variability. It depends on the number of genetic variants affecting a trait, their frequencies in the population, the magnitude of their effects and their interactions with each other and the environment. Defining the genetic architecture of a complex trait or disease is central to the scientific and clinical goals of human genetics, which are to understand disease aetiology and aid in disease screening, diagnosis, prognosis and therapy. Recent technological advances have enabled genome-wide association studies and emerging next-generation sequencing studies to begin to decipher the nature of the heritable contribution to traits and disease. Here, we describe the types of genetic architecture that have been observed, how architecture can be measured and why an improved understanding of genetic architecture is central to future advances in the field.

PMID:
29225335
DOI:
10.1038/nrg.2017.101
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center