White matter lesion progression: genome-wide search for genetic influences

Hofer, E. et al. (2015) White matter lesion progression: genome-wide search for genetic influences. Stroke, 46(11), pp. 3048-3057. (doi: 10.1161/STROKEAHA.115.009252) (PMID:26451028)

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BACKGROUND AND PURPOSE White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. METHODS Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies. RESULTS A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (P<5×10(-8)). Four loci were suggestive (P<1×10(-5)) of an association with WML progression: 10q24.32 (rs10883817, P=1.46×10(-6)); 12q13.13 (rs4761974, P=8.71×10(-7)); 20p12.1 (rs6135309, P=3.69×10(-6)); and 4p15.31 (rs7664442, P=2.26×10(-6)). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors, and baseline WML burden. CONCLUSIONS Common genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, lifestyle, or host-related biological factors.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Stott J, Professor David and Ford, Professor Ian and Sattar, Professor Naveed
Authors: Hofer, E., Cavalieri, M., Bis, J. C., DeCarli, C., Fornage, M., Sigurdsson, S., Srikanth, V., Trompet, S., Verhaaren, B. F. J., Wolf, C., Yang, Q., Adams, H. H. H., Amouyel, P., Beiser, A., Buckley, B. M., Callisaya, M., Chauhan, G., de Craen, A. J. M., Dufouil, C., van Duijn, C. M., Ford, I., Freudenberger, P., Gottesman, R. F., Gudnason, V., Heiss, G., Hofman, A., Lumley, T., Martinez, O., Mazoyer, B., Moran, C., Niessen, W. J., Phan, T., Psaty, B. M., Satizabal, C. L., Sattar, N., Schilling, S., Shibata, D. K., Slagboom, P. E., Smith, A., Stott, D. J., Taylor, K. D., Thomson, R., Töglhofer, A. M., Tzourio, C., van Buchem, M., Wang, J., Westendorp, R. G. J., Gwen Windham, B., Vernooij, M. W., Zijdenbos, A., Beare, R., Debette, S., Ikram, M. A., Jukema, J. W., Launer, L. J., Longstreth, W. T., Mosley, T. H., Seshadri, S., Schmidt, H., and Schmidt, R.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
Journal Name:Stroke
Publisher:American Heart Association
ISSN (Online):1524-4628

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