The role of regulatory variation in complex traits and disease

Frank W. Albert, Leonid Kruglyak

Research output: Contribution to journalLiterature reviewpeer-review

452 Scopus citations

Abstract

We are in a phase of unprecedented progress in identifying genetic loci that cause variation in traits ranging from growth and fitness in simple organisms to disease in humans. However, a mechanistic understanding of how these loci influence traits is lacking for the majority of loci. Studies of the genetics of gene expression have emerged as a key tool for linking DNA sequence variation to phenotypes. Here, we review recent insights into the molecular nature of regulatory variants and describe their influence on the transcriptome and the proteome. We discuss conceptual advances from studies in model organisms and present examples of complete chains of causality that link individual polymorphisms to changes in gene expression, which in turn result in physiological changes and, ultimately, disease risk.

Original languageEnglish (US)
Pages (from-to)197-212
Number of pages16
JournalNature Reviews Genetics
Volume16
Issue number4
DOIs
StatePublished - Apr 19 2015

Bibliographical note

Funding Information:
The authors thank members of L.K.’s laboratory and many colleagues for discussions. L.K. is supported by funds from the Howard Hughes Medical Institute, the US National Institutes of Health and the James S. McDonnell Foundation. F.W.A. was supported by the German Science Foundation (DFG).

Publisher Copyright:
© 2015 Macmillan Publishers Limited.

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