Cited by 156Genetic Associations and EpidemiologyGenetic Neurodegenerative DiseasesGenetic factors in colorectal cancer

Tandem repeat polymorphisms: modulators of disease susceptibility and candidates for ‘missing heritability’

Hannan, Anthony J.·2010·Trends in Genetics

Abstract

A problem of 'missing heritability' has been identified following recent genome-wide association (GWA) studies of single nucleotide polymorphisms (SNPs) associated with complex diseases. Current GWA studies fail to detect key sources of genetic variation, particularly tandem-repeat polymorphisms (TRPs), which provide a unique source of genetic variability by modulating a range of biological processes. Expanded tandem repeats cause various monogenic disorders, including Huntington's disease and various ataxias. However, there is emerging evidence suggesting that TRPs have a role in polygenic diseases. For example, candidate gene studies have found associations between specific TRPs and various brain disorders. Future GWA studies that include all TRPs as genetic variables will reveal the full extent of their association with complex diseases. TRPs might provide substantial genetic variability contributing to complex polygenic diseases and could be an important source of the missing heritability evident in SNP-based GWA studies.

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Crossref · 10.1016/j.tig.2009.11.008

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  • Missing ASD heritability may partly result from difficulty resolving repetitive DNA variants from short-read data.

    “the “missing heritability” could, in part, be attributed to the difficulty of resolving complex variants such as variations in repetitive regions of DNA from short-read next-generation sequence data24,25.”

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Authors
Hannan, A. J.
Affiliations
The University of Melbourne (AU)
Corresponding author
Hannan, Anthony J.
Venue
Trends in Genetics
Publisher
Elsevier BV
Published
2010-02
Volume
26
Issue
2
Pages
59-65
ISSN
0168-9525 (ISSN-L)
OpenAlex
W2161624819
Cited by
156
References
77
Citations by year
2026: 3 · 2025: 5 · 2024: 15 · 2023: 7 · 2022: 13 · 2021: 7 · 2020: 11 · 2019: 4 · 2018: 17 · 2017: 8 · 2016: 9 · 2015: 6 · 2014: 16 · 2013: 15 · 2012: 8
FWCI
0.63
Type
journal article
Language
en
Open access
closed
Locations
  • Trends in Genetics (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Pfizer Australia
  • National Health and Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords
tandem repeat polymorphism, missing heritability, disease susceptibility, single nucleotide polymorphisms, genome-wide association study, genetic variation, Huntington's disease, ataxia, brain disorders, candidate genes
MeSH terms
Humans, Polymorphism, Genetic, Evolution, Molecular, Genetic Predisposition to Disease, Tandem Repeat Sequences, Genome-Wide Association Study

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