Abdullah Sheikhi Curtin University of Technology 19th Twin Workshop Report 19th Twin and Family Studies Methodology Workshop Report Boulder 6th – 10 March 2006 Q: Submit a brief report (1-2 pages) detailing what is being learned or gained from attendance this workshop? The sessions I had from the workshop were enriched by various topics in the area of behavioural genetics and many of new skills have being learned from it. In the talk presented by Nick Martin about the Causes of Human variation I learned the different approaches about the analysis of the causes of human variability and the idea of variance which was developed by Fisher (1918). Also I had a historical overview about the pioneer people in this field from Darwin and Mendel in 1860s until 2000 by Michael Neal. Also I had an overview about the complex trait model and how the variance components can interact with each other. Furthermore, I had an idea about the designs to disentangle Genetic + Environment. Such as family studies, MZ twins alone, MZ twins reared apart, adoptions, MZ and DZ twins reared together, and extended twin design. Moreover, I had an introduction about the ACE Model for twin data and structural equation modeling. In the second session presented by Mike Neale and Hermine Maese titled “Summarizing Variation & Matrix algebra/ Introduction to Mx” I had the opportunity to learn more about the Mean, Variance, and Covariance and how can be calculated and how to estimate these parameter by Maximum Likelihood. Also I refreshed my memory about the use of Matrix Algebra and Normal Likelihood Theory. Also, I had an overview about how to get used to Mx script language such as the general comments, Job Structure, Group Structure, Read Observed Data, Matrix Declaration, Matrix Types: Matrices II and III, Constrained Matrices, Binary Matrix Operations, Matrix Operations Priorities, Matrix Functions, Specify Numbers/ Parameters. In the third talk by Danielle Dick gave the concept of Path Analysis which showed me how to represent linear models for the relationships between variables in diagrammatic form, and explained how path analysis can make it easy to derive expectation for the variances and covariances of variables in terms of the parameters proposed by the model. Also she showed how much path analysis can be easily translated into matrix form for use in programs such as Mx. The forth session titled “Univariate ACE Model” presented by Hermine Maes and Nick Martin, reviewed the basic elements of doing univariate genetic analysis. I have learned the difference between saturated models and Univariate Models and also the components of ACE and ADE models. Also, I had the opportunity to apply both models on actual data by estimating the variance components. In addition, I got my self familiar with the Mx script structures and commands. In the fifth presentation titled “Biometrical Genetics” given by Manuel Ferreira, I had the chance to know how to use the common genetic parameters such as allele frequencies, genetic effects, dominance, variance components, etc. in order to construct biometrical genetic model. Abdullah Sheikhi Curtin University of Technology 19th Twin Workshop Report In the sixth talk titled “Categorical Data“presented by Fruhling Rijsdijk and Kate Morley, I had an introduction about the Categorical Data and how can define liability and describe assumptions of the liability model. Also, I gained the skill about how heritability of liability can be estimated from categorical twin data. Furthermore, I learned how can I fit ordinal data in Mx as Mx has a built-in fit function for the maximum-likelihood analysis of 2-way Contingency tables analyses limited to only two variables. The seventh and eightieth sessions were talked about Heterogeneity presented by Hermine Maes and Danielle Posthuma, gave me a background about the contributions of additive genetic, dominance/shared environmental and unique environmental factors to the variance for both the Univariate Analysis and Heterogeneity Analysis, and also if there are different genetic/environmental factors influencing the trait in males and females. The ninth talk was about the Missing Data theory by Mike Neale. In this presentation I had the opportunity to know types of missing data and I learned the way to structure the missing data in Mx script The tenth presentation by Danielle Posthuma titled “Extended sibshihps”, explained to us the need to design an extended model of MZ or DZ twin with large sibships. I had the chance to practice how to include up to six sibs to the MZ and DZ twin pedigree, and checked the –2ll, df, estimated parameters, n observations for each model in Mx script. In addition, I exercised how to modify the Mx script for maximum nr of siblings = 3, 4, 5, or 6, in both univariate and bivariate models. The eleventh and twelfth presentations were by Manuel Ferreira and Sarah Medland titled „Introduction to the Principles of QTL Linkage analysis in Mx‟, which helps to localise and identify a locus that regulates a trait (QTL). From this talk I had the opportunity to strengthen my background about the difference between Parametric vs. Nonparametric Linkage Analysis, and to develop the concept of the two kinds of genotypic similarity between relatives; the IBS Alleles shared Identical By State “look the same”, and IBD Alleles shared Identical By Descent “a copy of the same ancestor allele”. In addition, I increased my knowledge about the Haseman-Elston regression for the Quantitative traits, Variance Components Maximum Likelihood for the Quantitative & Categorical traits, and genome-wide linkage analysis. I also had the opportunity to strengthen my skills on MERLIN to estimate IBD and allele frequency for a pedigree. In the thirteenth talk by Benjamin Neals titled „Association Analysis‟ I had a wide spectrum view about the strategies of association and linkage disequilibrium designs, including: linear Model of Association, types of Allelic Association, building haplotype maps (blocks) for gene-finding, biometrical model, regression model of association, family-based - Trio (TDT) design, sib-pairs/extended families (QTDT) design, and case-control design. I also had an overview about a wide range of statistical methods that applied with association from t-test to evolutionary model- based MCMC in order to correlate phenotypic and genotypic variability. Abdullah Sheikhi Curtin University of Technology 19th Twin Workshop Report The final talk was by Nick Martin titled „QTL studies: past, present and future‟. This presentation exhibited the significance role of the of the previous twin genetic strategies including AEC model by Mx, linkage and association. This had been exhibited by several MZ and DZ twin genetic studies on complex disorders such as Epilepsy, Schizophrenia, Depression and Asthma. Additionally, he talked about the effect of multivariate analysis on linkage power, and epigenetic discordance in identical twins. In conclusion, this workshop has acquired me the fundamentals about the phenotypic approaches on twins by using AEC univariate and multivariate twin designs by using Mx. Moreover, I have learned the basis of Linkage and association analyses that help to localise and identify genes that contributed to certain phenotypes including the human complex disorders. Finally, I would like to introduce my sincere thanks to the Australian Twin Registry for their funding to attend this workshop, which has helped me to gain new skills and knowledge on twin research.
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