The ‘Common Disease-Common Variant’ Hypothesis and Familial Risks
Open accessAbstract
The recent large genotyping studies have identified a new repertoire of disease susceptibility loci of unknown function, characterized by high allele frequencies and low relative risks, lending support to the common disease-common variant (CDCV) hypothesis. The variants explain a much larger proportion of the disease etiology, measured by the population attributable fraction, than of the familial risk. We show here that if the identified polymorphisms were markers of rarer functional alleles they would explain a much larger proportion of the familial risk. For example, in a plausible scenario where the marker is 10 times more common than the causative allele, the excess familial risk of the causative allele is over 10 times higher than that of the marker allele. However, the population attributable fractions of the two alleles are equal. The penetrance mode of the causative locus may be very difficult to deduce from the apparent penetrance mode of the marker locus.
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The rare allele model must explain population association data and fit demographic distributions within and among families, and there is little theory supporting that it can do both.
“Nevertheless, the rare allele model must not only explain association data in populations, but also fit demographic distributions of disease within and among families, and there is little theory supporting the claim that they can do both55–57.”
From Rare and common variants: twenty arguments (2012) · cites this paper as [57]
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- Authors
- Hemminki, K., Försti, A., & Bermejo, J. L.
- Affiliations
- German Cancer Research Center (DE)
- Corresponding author
- Hemminki, Kari
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-06-18
- Volume
- 3
- Issue
- 6
- Pages
- e2504
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2423486
- OpenAlex
- W2086501836
- Cited by
- 57
- References
- 24
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 1 · 2014: 5 · 2013: 2 · 2012: 8
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Forskningsrådet för Arbetsliv och Socialvetenskap
- Bundesministerium für Bildung und Forschung
- Cancerfonden
- Deutsche Krebshilfe
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Keywords
- common disease-common variant hypothesis, familial risk, disease susceptibility loci, population attributable fraction, marker alleles, functional alleles, penetrance, genetic association studies, allele frequency
- MeSH terms
- Alleles, Humans, Polymorphism, Genetic, Genetic Predisposition to Disease
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