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Combining Family and Twin Data in Association Studies to Estimate the Noninherited Maternal Antigens Effect
Author(s) -
Balliu Brunilda,
Tsonaka Roula,
van der Woude Diane,
Boehringer Stefan,
HouwingDuistermaat Jeanine J.
Publication year - 2012
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.21667
Subject(s) - odds ratio , offspring , odds , statistics , medicine , demography , mathematics , biology , genetics , logistic regression , pregnancy , sociology
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 ( C J L ) approach. Simulations show that the C J L 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).