The ‘Common Disease-Common Variant’ Hypothesis …

So am I then arguing in favor of the CDCV hypotheis? Of course not– rare variants, aside from being predictive for disease in some individuals, also give important insight into the biology of the disease. But it is possible right now, using genome-wide SNP arrays and databases like the HapMap, to search the entire genome for common variants that contribute to disease. This is an essential step–finding the alleles that contribute disproportionately to the population-level risk for a disease. Eventually, to a point where rare variants can also be assayed on a genome-wide, high-throughput scale, but that’s not the case yet. Once it is, expect the CDRV hypothesis to be trumpted as right all along.

the common disease-common variant hypothesis

The idea behind these studies is the common disease/common variant (CDCV) ..

The ‘Common Disease-Common Variant ’ Hypothesis …

In order to substantiate claims about the role of either specific common or rare variations in disease, some form of validation of an initial finding implicating those variations is in order. For common variations implicated in GWA and candidate gene association studies, the sine qua non of validation is replication of the association in an independent population or sample of individuals than that used in the initial study []. However, replication studies of associations involving rare variations that exploit follow-up or ancillary populations is problematic given the infrequency of the variations of interest. This fact can be overcome to some degree by testing the hypothesis that the genes or genomic regions of interest have a collection of variations that, as a group, are more frequent among individuals with a disease phenotype than individuals without that phenotype (). Statistical methods for carrying out such hypothesis tests are in their infancy, but will be crucial for advancing the CDRV hypothesis [, , ]. In addition to statistical evidence for associations between variations and a disease phenotype (whether implicating common or rare variations, or whether identified in an initial or replication study), it is important to assess the biological significance of the variation(s) in question via computational methods, laboratory assays or model systems.

(common disease–common variant, CDCV, hypothesis), ..

In order to substantiate claims about the role of either specific common or rare variations in disease, some form of validation of an initial finding implicating those variations is in order. For common variations implicated in GWA and candidate gene association studies, the sine qua non of validation is replication of the association in an independent population or sample of individuals than that used in the initial study []. However, replication studies of associations involving rare variations that exploit follow-up or ancillary populations is problematic given the infrequency of the variations of interest. This fact can be overcome to some degree by testing the hypothesis that the genes or genomic regions of interest have a collection of variations that, as a group, are more frequent among individuals with a disease phenotype than individuals without that phenotype (). Statistical methods for carrying out such hypothesis tests are in their infancy, but will be crucial for advancing the CDRV hypothesis [, , ]. In addition to statistical evidence for associations between variations and a disease phenotype (whether implicating common or rare variations, or whether identified in an initial or replication study), it is important to assess the biological significance of the variation(s) in question via computational methods, laboratory assays or model systems.

30.01.2008 · The ‘Common Disease-Common Variant’ Hypothesis and Familial Risks
lending support to the common disease-common variant (CDCV) hypothesis.

disease, common variant hypothesis (CDCV)

The ‘Common Disease, Rare Variant (CDRV)’ hypothesis, on the contrary, argues that multiple rare DNA sequence variations, each with relatively high penetrance, are the major contributors to genetic susceptibility to common diseases.

07/08/2017 · The ‘Common Disease-Common Variant’ Hypothesis and Familial Risks

Common disease, common variant hypothesis

In silico genotypes. The Icelandic population is unique in several respects. For one, this population is a founder population with a known and well-documented family history. Therefore, the connection of virtually every Icelander to the founder population and the relatedness between different individuals can be assessed. When combined with systematic medical data that can be assessed, this population provides a powerful tool for genetic studies. The company is using this knowledge on family structure and available medical data to systematically screen for genes associated with disease. For example, the known family structures in Iceland provides the unique opportunity to infer genotypes in family members without actually genotyping them. These virtual genotypes appear to be highly reliable.

19/09/2016 · Common disease–common variant hypothesis (CDCV hypothesis)

This is the basis of the Common Disease/Common Variant (CDCV) ..

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.