Dataset Information

Variance of age-specific log incidence decomposition (VALID): a unifying model of measured and unmeasured genetic and non-genetic risks.

ABSTRACT:

Background

The extent to which known and unknown factors explain how much people of the same age differ in disease risk is fundamental to epidemiology. Risk factors can be correlated in relatives, so familial aspects of risk (genetic and non-genetic) must be considered.

Development

We present a unifying model (VALID) for variance in risk, with risk defined as log(incidence) or logit(cumulative incidence). Consider a normally distributed risk score with incidence increasing exponentially as the risk increases. VALID's building block is variance in risk, Δ2, where Δ = log(OPERA) is the difference in mean between cases and controls and OPERA is the odds ratio per standard deviation. A risk score correlated r between a pair of relatives generates a familial odds ratio of exp(rΔ2). Familial risk ratios, therefore, can be converted into variance components of risk, extending Fisher's classic decomposition of familial variation to binary traits. Under VALID, there is a natural upper limit to variance in risk caused by genetic factors, determined by the familial odds ratio for genetically identical twin pairs, but not to variation caused by non-genetic factors.

Application

For female breast cancer, VALID quantified how much variance in risk is explained-at different ages-by known and unknown major genes and polygenes, non-genomic risk factors correlated in relatives, and known individual-specific factors.

Conclusion

VALID has shown that, while substantial genetic risk factors have been discovered, much is unknown about genetic and familial aspects of breast cancer risk especially for young women, and little is known about individual-specific variance in risk.

SUBMITTER: Hopper JL

PROVIDER: S-EPMC10655167 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Variance of age-specific log incidence decomposition (VALID): a unifying model of measured and unmeasured genetic and non-genetic risks.

Hopper John L JL Dowty James G JG Nguyen Tuong L TL Li Shuai S Dite Gillian S GS MacInnis Robert J RJ Makalic Enes E Schmidt Daniel F DF Bui Minh M Stone Jennifer J Sung Joohon J Jenkins Mark A MA Giles Graham G GG Southey Melissa C MC Mathews John D JD

International journal of epidemiology 20231001 5

<h4>Background</h4>The extent to which known and unknown factors explain how much people of the same age differ in disease risk is fundamental to epidemiology. Risk factors can be correlated in relatives, so familial aspects of risk (genetic and non-genetic) must be considered.<h4>Development</h4>We present a unifying model (VALID) for variance in risk, with risk defined as log(incidence) or logit(cumulative incidence). Consider a normally distributed risk score with incidence increasing exponen ...[more]

PMID: 37349888

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Dataset Information

Variance of age-specific log incidence decomposition (VALID): a unifying model of measured and unmeasured genetic and non-genetic risks.

Background

Development

Application

Conclusion

Publications

Variance of age-specific log incidence decomposition (VALID): a unifying model of measured and unmeasured genetic and non-genetic risks.

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