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MBPhD Programme

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TAN, Geoffrey Chern-Ye

Entered:

2006

Current Position:

Qualified 2012

PhD title:

The genetics of individual differences in cognition and brain structure

Principal Supervisor:

Professor Richard Frackowiak, The Institute of Neurology

Funding Source:

Agency of Science, Technology and Research  (A*STAR) in Singapore.

Description of Project:

Purpose/ Primary end point: Finding common genetic influences on brain structure and the specific structural differences they cause. Secondary end points: Common genetic influences on aspects of cognition such as intelligence, executive function, personality and gender differences, and characterizing their relationship to brain structure. Characterising measures of individual difference in brain structure, decision-making and reaction time. Determining the interaction between environment and genetics in individual variability. Background: Earlier MRI studies with twins have shown that genetics is an important factor in individual variability of brain structure. Indeed, the volumes of the brain, grey matter and white matter have heritabilities between 80% and 90%, while patterns of heritability in brain structure have been mapped1. Areas of cognition such as general intelligence and executive function, as well as 2D:4D ratio also have heritabilities estimated at 70-85%2,3. Design and Methodology: Previous healthy volunteers with structural brain scans kept at the Wellcome Trust Centre for Neuroimaging will be contacted via email. Interested participants will be invited to book an appointment and will be sent a copy of the information sheets and consent form. After consent for the study and access to their scans is obtained, volunteers will complete a health screening questionnaire. Volunteers will perform additional tests involving motor reaction time, simple tests of general cognitive ability and a photocopy of their hands will be made for measurements of 2 digit to 4 digit ratio, a reflection of prenatal testosterone levels. Finally, blood samples will be obtained by venepuncture. Additionally, subjects will be invited to complete questionnaires on personality and preference via a confidential website. Mitochondrial and genomic DNA will be extracted from these blood samples stored in the Neurogenetics Unit at the Institute of Neurology. Analysis techniques: The genetic analysis of our DNA samples will be based on a genome-wide and candidate approaches looking for single nucleotide polymorphisms and copy number variants. 1000 volunteers will be recruited with T1-weighted structural MRI scans will be obtained for these individuals. Statistical comparisons will be performed on scans between variants at each SNP using voxel-based morphometry. Expected Outcomes: Determination of alleles significantly associated with measures of brain structure and cognition.

1. Thompson PM et al (2001) Genetic influences on brain structure. Nature Neuroscience 4, 1253-1258 (2)

2. Deary IJ et al (2006) Genetics of intelligence. European Journal of Human Genetics 14, 690-700 (3)

3. Paul SN et al (2006) Heritability of the Second to Fourth Digit Ratio: A Twin study. Twin Research and Human Genetics 9(2), 215-219 (4)

4. Buckholtz JW et al (2007) Allelic variation in RGS4 impacts functional and structural connectivity in the human brain. Journal of Neuroscience 27(7), 1584-1593

Publications: