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Master Thesis

Étude de l’héritabilité des marqueurs structurels mesurés en IRM cérébrale chez le sujet jeune dans la cohorte i-Share

Abstract : Introduction: Mounting evidence suggests that early life factors play a crucial role in the occurrence of late-life neurological diseases. The main aim of this study was to estimate the heritability of various structural brain MRI-markers in young adults from the i-Share cohort. The secondary aim was to identify the genetic correlation (or shared heritability) between structural brain MRI-markers in young adults (i-Share) and older adults (3C-Dijon population-based cohort). Methods: We studied the heritability of 350 MRI-markers of the brain structure in 1,464 participants from the i-Share cohort and of 51 MRI-markers (available in both studies) in the 3C-Dijon cohort (n=1,366), using the GCTA-GREML approach. We then studied the genetic correlation for these 51 MRI-markers between both populations using the GCTA-bivariate GREML approach. Results: Of the 350 MRI-markers studied, 76 were significantly heritable at the 5% threshold and belonged to three groups: cortical measurements, global volumes and subcortical volumes. Of these 76 markers, six passed the threshold corrected for multiple testing, including gray matter volumes of the hippocampus (total, left and right), the total gray matter volume of the caudate nucleus, that of the right pallidum and the total intracranial volume. Among the six significantly heritable MRI-markers after multiple testing in young adults, significant genetic correlations between young and older adults were found for gray matter volume of the right hippocampus and for total intracranial volume, although these volumes were not significantly heritable in the 3C-Dijon cohort. Four additional markers showed a significant genetic correlation between young and older adults: two measurements of the brainstem volume, the right caudate nucleus gray matter volume, and the volume of gray matter of the right transverse temporal cortex. Conclusion: In total we found that MRI-markers of brain structure in young adults were often heritable despite a limited sample size, the most significant heritability being observed for gray matter volumes of the hippocampus, the caudate nucleus and the right pallidum and total intracranial volume. Significant genetic correlations between young and older adults were found for gray matter volumes of the hippocampus, the right caudate nucleus, and the right transverse temporal cortex.
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Master Thesis
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Quentin Le Grand. Étude de l’héritabilité des marqueurs structurels mesurés en IRM cérébrale chez le sujet jeune dans la cohorte i-Share. Santé publique et épidémiologie. 2019. ⟨dumas-02435211⟩

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