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Chromosome X-wide association analysis and investigation of dosage compensation in sexually dimorphic phenotypes


About This PhD Project

Project Description

Rationale
Sex chromosomes have often been overlooked in genome-wide association studies due to the extra effort required for analysing them or misconceptions about their role in disease risk. However, they could represent one potential source for the “missing heritability” for complex phenotypes, especially for sexually dimorphic phenotypes, such as psychiatric disorders. Psychiatric disorders and psychiatric traits (psychiatric symptoms present in individuals from the general population without a disorder diagnosis) are one of the most striking examples of sexual dimorphism in population health and will be investigated in terms of their X chromosome associations and X chromosome inactivation. Up to 15% X chromosome genes escape from X inactivation and a recent X chromosome association analysis identified a locus for height which is not compensated between men and women.

Aims & Objectives
Identify X chromosome loci involved in sexually dimorphic phenotypes in ALSPAC with the possibility of using data from other cohorts that the MRC IEU already collaborates with.
Estimate the variance explained by X chromosome for sexually dimorphic phenotypes in males and females
Identify loci escaping X chromosome inactivation

Methods
Methods that will be used include genetic association analysis and meta-analysis, genome-wide complex trait analysis, polygenic risk scores, Bayesian frameworks, expression analysis.

References

Tukiainen et al. (2014) PLoS Genet 10(2): e1004127.
Wise et al (2013) Am J Hum Genet 92: 643–647.
Yang et al. (2011) Nat Genet 43: 519–525.

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