Projects per year
Methods: We applied HRHM to GS:SFHS, a large family and population based
Scottish cohort (N=19,896). Single-SNP and haplotype-based association tests were used to localize the association signal within the regions identified by HRHM. Functional prediction was used to investigate the effect of MDD-associated SNPs within the regions.
Results: A haplotype block across a 24kb region within the TOX2 gene reached genome-wide significance in HRHM. Single-SNP and haplotype-based association tests demonstrated that five out of nine genotyped SNPs and two haplotypes within this block were significantly associated with MDD. The expression of TOX2 and a brain-specific LncRNA RP1-269M15.3 in frontal cortex and Nucleus accumbens basal ganglia, respectively, were significantly regulated by MDD-associated SNPs within this region. Both the regional heritability and single SNP-associations within this block were replicated in the UK-Ireland group of the most recent release of the Psychiatric Genomics consortium (PGC2-MDD). The SNP-association was also replicated in a depressive symptom sample that shares some individuals with PGC2-MDD.
Conclusion: This study highlights the value of HRHM for MDD and provides an important target within TOX2 for further functional studies.
|Early online date||16 Dec 2016|
|Publication status||Published - 1 Sep 2017|
FingerprintDive into the research topics of 'Genome-wide regional heritability mapping identifies a locus within the TOX2 gene associated with Major Depressive Disorder'. Together they form a unique fingerprint.
- 3 Finished
Stratifying Resilience and Depression Longitudinally
McIntosh, A., Deary, I., Evans, K., Haley, C. & Porteous, D.
1/01/15 → 30/06/21
RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.
Deary, I., Gale, C., Holmes, M., Logie, P., Maclullich, A., Porteous, D., Seckl, J., Starr, J., Wardlaw, J. & Okely, J.
1/09/13 → 31/08/19
UK central government bodies/local authorities, health and hospital authorities
1/04/11 → 31/03/14