* The impact of age on genetic risk for common diseases.
- Inherited genetic variation contributes to individual risk for many complex diseases and is increasingly being used for predictive patient stratification. Previous work has shown that genetic factors are not equally relevant to human traits across age and other contexts, though the reasons for such variation are not clear. Here, we introduce methods to infer the form of the longitudinal relationship between genetic relative risk for disease and age and to test whether all genetic risk factors behave similarly. We use a proportional hazards model within an interval-based censoring methodology to estimate age-varying individual variant contributions to genetic relative risk for 24 common diseases within the British ancestry subset of UK Biobank, applying a Bayesian clustering approach to group variants by their relative risk profile over age and permutation tests for age dependency and multiplicity of profiles. We find evidence for age-varying relative risk profiles in nine diseases, including hypertension, skin cancer, atherosclerotic heart disease, hypothyroidism and calculus of gallbladder, several of which show evidence, albeit weak, for multiple distinct profiles of genetic relative risk. The predominant pattern shows genetic risk factors having the greatest relative impact on risk of early disease, with a monotonic decrease over time, at least for the majority of variants, although the magnitude and form of the decrease varies among diseases. As a consequence, for diseases where genetic relative risk decreases over age, genetic risk factors have stronger explanatory power among younger populations, compared to older ones. We show that these patterns cannot be explained by a simple model involving the presence of unobserved covariates such as environmental factors. We discuss possible models that can explain our observations and the implications for genetic risk prediction.
=>1.損害の恐れ, 危険, 冒険, リスク, 2.危険にさらす, 3.敢えてする, 被保険者, 被保険物, 危険にさらす,
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Overview of noun risk
The noun risk has 4 senses (first 2 from tagged texts)
1. (4) hazard, jeopardy, peril, risk, endangerment -- (a source of danger; a possibility of
incurring loss or misfortune; "drinking alcohol is a health hazard")
2. (2) risk, peril, danger -- (a venture undertaken without regard to possible loss or injury; "he
saw the rewards but not the risks of crime"; "there was a danger he would do the wrong thing")
3. risk, risk of infection -- (the probability of becoming infected given that exposure to an
infectious agent has occurred)
4. risk, risk of exposure -- (the probability of being exposed to an infectious agent)
Overview of verb risk
The verb risk has 2 senses (first 2 from tagged texts)
1. (8) risk, put on the line, lay on the line -- (expose to a chance of loss or damage; "We risked
losing a lot of money in this venture"; "Why risk your life?"; "She laid her job on the line when
she told the boss that he was wrong")
2. (2) gamble, chance, risk, hazard, take chances, adventure, run a risk, take a chance -- (take a
risk in the hope of a favorable outcome; "When you buy these stocks you are gambling")
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