Replication in genetic studies of complex traits

Sillanpää, Mikko J.; Auranen, Kari

doi:10.1046/j.1529-8817.2004.00122.x

Cited by 49 publications

(42 citation statements)

References 127 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In general, this test performs well for two-sided hypotheses if the sample size is large because the distribution of LRTs then follows a chi-square distribution, asymptotically. On the other hand, when the amount of data increases, all hypotheses eventually become statistically significant (Sillanpää and Auranen 2004) and, for bounded parameters like variance components, the null distribution might be difficult to estimate in general (Crainiceanu and Ruppert 2004). Consequently, in these situations, approximating the distribution of LRTs using a chi-square distribution can give incorrect results.…”

Section: Discussionmentioning

confidence: 99%

Efficient Markov Chain Monte Carlo Implementation of Bayesian Analysis of Additive and Dominance Genetic Variances in Noninbred Pedigrees

Waldmann¹,

Hallander²,

Hoti

et al. 2008

Genetics

View full text Add to dashboard Cite

Accurate and fast computation of quantitative genetic variance parameters is of great importance in both natural and breeding populations. For experimental designs with complex relationship structures it can be important to include both additive and dominance variance components in the statistical model. In this study, we introduce a Bayesian Gibbs sampling approach for estimation of additive and dominance genetic variances in the traditional infinitesimal model. The method can handle general pedigrees without inbreeding. To optimize between computational time and good mixing of the Markov chain Monte Carlo (MCMC) chains, we used a hybrid Gibbs sampler that combines a single site and a blocked Gibbs sampler. The speed of the hybrid sampler and the mixing of the single-site sampler were further improved by the use of pretransformed variables. Two traits (height and trunk diameter) from a previously published diallel progeny test of Scots pine (Pinus sylvestris L.) and two large simulated data sets with different levels of dominance variance were analyzed. We also performed Bayesian model comparison on the basis of the posterior predictive loss approach. Results showed that models with both additive and dominance components had the best fit for both height and diameter and for the simulated data with high dominance. For the simulated data with low dominance, we needed an informative prior to avoid the dominance variance component becoming overestimated. The narrow-sense heritability estimates in the Scots pine data were lower compared to the earlier results, which is not surprising because the level of dominance variance was rather high, especially for diameter. In general, the hybrid sampler was considerably faster than the blocked sampler and displayed better mixing properties than the single-site sampler.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficient Markov Chain Monte Carlo Implementation of Bayesian Analysis of Additive and Dominance Genetic Variances in Noninbred Pedigrees

Waldmann¹,

Hallander²,

Hoti

et al. 2008

Genetics

View full text Add to dashboard Cite

show abstract

“…Lack of confirmation should not be interpreted as exclusion of these other regions. Factors such as differences in the definition of the RWR phenotype may affect the results, as may ascertainment procedures used to obtain the families (Sillanpää and Auranen, 2004), and the well-known requirement for greater sample sizes in replication studies than in the original sample noted by Suarez et al (1994).…”

Section: Discussionmentioning

confidence: 99%

Genomewide scan for real‐word reading subphenotypes of dyslexia: Novel chromosome 13 locus and genetic complexity

Igo

Chapman

Berninger

et al. 2005

American J of Med Genetics Pt B

View full text Add to dashboard Cite

Dyslexia is a common learning disability exhibited as a delay in acquiring reading skills despite adequate intelligence and instruction. Reading single real words (real-word reading, RWR) is especially impaired in many dyslexics. We performed a genome scan, using variance-components (VC) linkage analysis and Bayesian Markov chain Monte Carlo (MCMC) joint segregation and linkage analysis, for three quantitative measures of RWR in 108 multigenerational families, with followup of the strongest signals with parametric LOD score analyses. We used single-word reading efficiency (SWE) to assess speed and accuracy of RWR, and word identification (WID) to assess accuracy alone. Adjusting SWE for WID provided a third measure of RWR efficiency.All three methods of analysis identified a strong linkage signal for SWE on chromosome 13q. Based on multipoint analysis with 13 markers we obtained a MCMC intensity ratio of 53.2 (chromosome-wide p < 0.004), a VC LOD score of 2.29, and a parametric LOD score of 2.94, based on a quantitative-trait model from MCMC segregation analysis. A weaker signal for SWE on chromosome 2q occurred in the same location as a significant linkage peak seen previously in a scan for phonological decoding. MCMC oligogenic segregation analysis identified three models of transmission for WID, which could be assigned to two distinct linkage peaks on chromosomes 12 and 15. Taken together, these results indicate a locus for efficiency and accuracy of RWR on chromosome 13, and a complex model for inheritance of RWR accuracy with loci on chromosomes 12 and 15.

show abstract

“…Researchers have attributed the variable associations and poor replication rates to small samples producing a low statistical power, the use of different methodological approaches to detect genetic variants, imprecisely defined phenotypes, genetic heterogeneity, differences in allele frequencies and complex traits of SLE characterized by non-Mendelian inheritance. 1 More than 700 genetic studies on SLE have been published. Although there have been many genetic studies of SLE in Asia, their precise number and types and the consistency of their findings remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Genetic studies of systemic lupus erythematosus in Asia: where are we now?

Kim

et al. 2009

Genes Immun

View full text Add to dashboard Cite

There have been many genetic studies of systemic lupus erythematosus (SLE) in Asia, but the status of SLE in Asia remains unclear. Genes that have been associated with SLE in Caucasians have shown both consistent and inconsistent results in Asians. This prompted us to review studies of SLE-associated genes and compare the degree of consistency according to ethnicity in Asia. We searched PubMed and the national databases in Korea and Japan for SLE genetic studies. A total of 755 articles were found and after applying various exclusion criteria, 442 studies including 17 linkage studies, 2 genome-wide association studies and 423 candidate-gene analyses were reviewed. Nine linkage loci were confirmed to be associated with SLE susceptibility in non-Asians, but the risk locus (16q12) has been identified in only one Asian study. A total of 156 candidate genes were analyzed, of which 92 were studied in Asians. Although there were allelic (HLA-DRB1 and IRF5) or genetic heterogeneity (FCGR gene family), HLA-DRB1, the FCGR gene family, IRF5, STAT4 and MECP2 showed consistent associations with SLE susceptibility across ethnicities. In conclusion, genetic associations often vary with ethnicity, requiring validation in different ethnic groups, and hence future SLE genetic studies will require strong worldwide collaborations.

show abstract

Replication in genetic studies of complex traits

Cited by 49 publications

References 127 publications

Efficient Markov Chain Monte Carlo Implementation of Bayesian Analysis of Additive and Dominance Genetic Variances in Noninbred Pedigrees

Efficient Markov Chain Monte Carlo Implementation of Bayesian Analysis of Additive and Dominance Genetic Variances in Noninbred Pedigrees

Genomewide scan for real‐word reading subphenotypes of dyslexia: Novel chromosome 13 locus and genetic complexity

Genetic studies of systemic lupus erythematosus in Asia: where are we now?

Contact Info

Product

Resources

About