English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

The case-control design is often used to test associations between thecase-control status and genetic variants. In addition to this primary phenotypea number of additional traits, known as secondary phenotypes, are routinelyrecorded and typically associations between genetic factors and these secondarytraits are studied too. Analysing secondary phenotypes in case-control studiesmay lead to biased genetic effect estimates, especially when the marker testedis associated with the primary phenotype and when the primary and secondaryphenotypes tested are correlated. Several methods have been proposed in theliterature to overcome the problem but they are limited to case-control studiesand not directly applicable to more complex designs, such as the multiple-casesfamily studies. A proper secondary phenotype analysis, in this case, iscomplicated by the within families correlations on top of the biased samplingdesign. We propose a novel approach to accommodate the ascertainment processwhile explicitly modelling the familial relationships. Our approach pairsexisting methods for mixed-effects models with the retrospective likelihoodframework and uses a multivariate probit model to capture the associationbetween the mixed type primary and secondary phenotypes. To examine theefficiency and bias of the estimates we performed simulations under severalscenarios for the association between the primary phenotype, secondaryphenotype, and genetic markers. We will illustrate the method by analysing theassociation between triglyceride levels and glucose (secondary phenotypes) andgenetic markers from the Leiden Longevity study, a multiple-cases family studythat investigates longevity.

Secondary Phenotype Analysis in Ascertained Family Designs: Application to the Leiden Longevity Study