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- Title
Joint detection of association, imprinting and maternal effects using all children and their parents.
- Authors
Han, Miao; Hu, Yue-Qing; Lin, Shili
- Abstract
Genomic imprinting and maternal effects have been increasingly explored for their contributions to complex diseases. Statistical methods have been proposed to detect both imprinting and maternal effects simultaneously based on nuclear families. However, these methods only make use of case-parents triads and possibly control-parents triads, thus wasting valuable information contained in the siblings. More seriously, most existing methods are full-likelihood based and have to make strong assumptions concerning mating-type probabilities (nuisance parameters) to avoid over-parametrization. In this paper, we develop a partial Likelihood approach for detecting Imprinting and Maternal Effects (LIME), using nuclear families with an arbitrary number of affected and unaffected children. By matching affected children with unaffected ones (within or across families) having the same triad/pair familial genotype combination, we derive a partial likelihood that is free of nuisance parameters. This alleviates the need to make strong, yet unrealistic assumptions about the population, leading to a procedure that is robust to departure from Hardy-Weinberg equilibrium. Power gain by including siblings and robustness of LIME under a variety of settings are demonstrated. Our simulation study also indicates that it is more profitable to recruit additional siblings than additional families when the total number of individuals is kept the same. We applied LIME to the Framingham Heart Study data to demonstrate its utility in analyzing real data. Many of our findings are consistent with results in the literature; potentially novel genes for hypertension have also emerged.
- Subjects
GENOMIC imprinting; NUCLEAR families; HEREDITY; CHILDREN; PARENTS
- Publication
European Journal of Human Genetics, 2013, Vol 21, Issue 12, p1449
- ISSN
1018-4813
- Publication type
Article
- DOI
10.1038/ejhg.2013.49