Chortle There are many different kinds of laughter. Boff When delivering a punch line, comedic performers want nothing more than to elicit a boff. Titter Far from a belly laugh or a hearty guffaw, a titter is a nervous or self-conscious laugh. Giggle Before English speakers were tittering, they were giggling.
In this work, our main focus was to see whether modeling longitudinal data could provide helpful information to increase the power of detecting true SNVs when compared with the methods for analyzing data at one time point. Here we directly applied the original genotype data into modeling and illustrated that the longitudinal repeated observations were indeed helpful to detect DBP-related genetic factors. However, many true SNVs are rare variants, some of which could have big allelic effect for specific individuals when the disease mutation presents.
As a result of small minor allele frequency MAF , the association between such rare variants and their corresponding phenotypes is still weak at the population level [ 1 ].
This may be one of the main reasons why the overall power is low in detecting the majority of the causal or regulatory genetic factors. Various strategies of rare-variant collapsing procedures [ 14 , 15 ] could be applied to grouping and combining genotypes of rare variants, which has potential to further increase the power.
The computational speed of the multilevel model is comparable with the linear mixed-effects model estimation by lmekin. Both models are computationally demanding e. However, we observed that the convergence speed of the iterative generalized least squares algorithm for the multilevel model is relatively fast: the results usually do not change much after two iterations.
So, restricting the number of iterations could potentially reduce computational time. Further study on improving computation efficiency will be carried out in the near future. We developed a multilevel model for fitting family-based genotype data and repeated measures of covariates to quantitative longitudinal response, which accounts for correlations among individuals, nesting effects at the family and individual levels, and the time series correlations due to the repeated measures of covariates and responses.
Using the simulated data of GAW18, this method showed more accurate type I error control than the LME model by lmekin, which is likely the result of better account for correlations among individuals.
The multilevel model also provided higher power at small p- value cutoffs. At the same time, both lmekin and multilevel model, which use the longitudinal information, have higher power than GWAF, which only models data at one time point.
ZW designed the overall study. All authors read and approved the final manuscript. Publication charges for this supplement were funded by the Texas Biomedical Research Institute. National Center for Biotechnology Information , U. BMC Proc. Published online Jun Author information Article notes Copyright and License information Disclaimer. Corresponding author. Taoye Chen: ude. Supplement Genetic Analysis Workshop This article has been cited by other articles in PMC.
Abstract Compared with microarray-based genotyping, next-generation whole genome sequencing WGS studies have the strength to provide greater information for the identification of rare variants, which likely account for a significant portion of missing heritability of common human diseases.
Background Whole genome sequencing WGS provides comprehensive collection of genetic variations and thus is promising in discovering novel inheritable factors for both Mendelian and complex traits. Methods Method 1: LME model Linear mixed-effects models offer a natural approach to deal with correlation structures among observations. Method 2: Multi-level model We extend the classic multi-level model [ 4 , 5 , 11 ] to analyze WGS family data with longitudinal repeated measures. Results For evaluating the methods, we used the "dose" genotype data of the true single-nucleotide variants SNVs on chromosome 3 that were associated with diastolic blood pressure DBP in simulation replicates.
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