The 'common Disease-common Variant' Hypothesis and Familial Risks

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2008 Jun 19

PMID 18560565

Citations 30

Authors

Kari Hemminki

Asta Forsti

Justo Lorenzo Bermejo

Affiliations

Soon will be listed here.

Abstract

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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