Tandem repeat polymorphisms: modulators of disease susceptibility and candidates for ‘missing heritability’
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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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.”
From Genome-wide detection of tandem DNA repeats that are expanded in autism (2020) · cites this paper as [24]
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- Authors
- Hannan, A. J.
- Affiliations
- The University of Melbourne (AU)
- Corresponding author
- Hannan, Anthony J.
- ORCID
- 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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