Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/116916

Documents

In Collections

This item can be found in the following collections:

Balliu, B.; Tsonaka, R.; Woude, D. van der; Boehringer, S.; Houwing-Duistermaat, J.J. (2012)

Combining Family and Twin Data in Association Studies to Estimate the Noninherited Maternal Antigens Effect

Article / Letter to editor
It is hypothesized that certain alleles can have a protective effect not only when inherited by the offspring but also as noninherited maternal antigens (NIMA). To estimate the NIMA effect, large samples of families are needed. When large samples are not available, we propose a combined approach to estimate the NIMA effect from ascertained nuclear families and twin pairs. We develop a likelihood-based approach allowing for several ascertainment schemes, to accommodate for the outcome-dependent sampling scheme, and a family-specific random term, to take into account the correlation between family members. We estimate the parameters using maximum likelihood based on the combined joint likelihood (CJL) approach. Simulations show that the CJL is more efficient for estimating the NIMA odds ratios as compared to a families-only approach. To illustrate our approach, we used data from a family and a twin study from the United Kingdom on rheumatoid arthritis, and confirmed the protective...Show moreIt is hypothesized that certain alleles can have a protective effect not only when inherited by the offspring but also as noninherited maternal antigens (NIMA). To estimate the NIMA effect, large samples of families are needed. When large samples are not available, we propose a combined approach to estimate the NIMA effect from ascertained nuclear families and twin pairs. We develop a likelihood-based approach allowing for several ascertainment schemes, to accommodate for the outcome-dependent sampling scheme, and a family-specific random term, to take into account the correlation between family members. We estimate the parameters using maximum likelihood based on the combined joint likelihood (CJL) approach. Simulations show that the CJL is more efficient for estimating the NIMA odds ratios as compared to a families-only approach. To illustrate our approach, we used data from a family and a twin study from the United Kingdom on rheumatoid arthritis, and confirmed the protective NIMA effect, with an odds ratio of 0.477 (95% CI 0.264-0.864).Show less
ascertainment
family studies
joint likelihood
mixed models
NIMA
twin studies
All authors
Balliu, B.; Tsonaka, R.; Woude, D. van der; Boehringer, S.; Houwing-Duistermaat, J.J.
Date
2012
Journal
Genetic Epidemiology
Pages
811 - 819
DOI
doi:10.1002/gepi.21667