Post doc Sudheer Giddaluru

Genome wide genetic association studies of brain imaging and cognitive phenotypes.

Post doc Sudheer Giddaluru

The major focus of the projects I work on is to identify the genetic factors underlying cognitive processes and brain imaging measures in healthy individuals. An approach of cognitive and brain imaging measures as intermediate or endophenotypes for major psychiatric illnesses has long been suggested. Such studies may help us to understand the factors mediating the effects of genetic risk variants to psychiatric illnesses as these disorders are often accompanied by severe cognitive deficits.


Large sample genotyping

In an ongoing study we have performed a genome wide association study (GWAS) of white matter (WM) microstructural coherence as indexed by a whole-brain WM fractional anisotropy (FA) derived from diffusion tensor imaging (DTI).

In a genome wide association study single nucleotide polymorphisms (SNPs), the most abundant and stable variation found in the genome, covering the whole genome are genotyped in large samples of individuals. Each SNP variation is then tested for statistical association with a quantifiable phenotype. FA in brain characterizes the structural integrity of the myelin sheath. Myelin ensheathment of axons provides electrical insulation, which is necessary for synchronized information processing in the brain. For FA, we have successfully identified a total 50 single nucleotide variants at 12 different chromosomal locations showing significance of association at Meta P-value < 10-6.

 

Processing speed task

Information processing is a fundamental capacity and correlates with performance on different cognitive tasks. We further conducted a second GWAS on a processing speed task. For processing speed we have identified 7 different chromosomal loci with variants showing association Meta P-value < 10-6. We further tested if some of the genes linked to processing speed may also be associated with FA and found three genes to be associated with both FA and speed with Fisher’s combined P-value < 10-6.


Several of the genes identified in this study have previously been implicated in CNS-related function such as neuronal development and a locus implicated in schizophrenia. Further, we have identified the FA results to be enriched for gene sets relevant in myelination in the central nervous system.

 

Publisert 10. okt. 2014 09:53 - Sist endret 9. apr. 2015 13:16