@article {6861, title = {White Matter Lesion Progression: Genome-Wide Search for Genetic Influences.}, journal = {Stroke}, volume = {46}, year = {2015}, month = {2015 Nov}, pages = {3048-57}, abstract = {

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{\texttimes}10(-8)). Four loci were suggestive (P<1{\texttimes}10(-5)) of an association with WML progression: 10q24.32 (rs10883817, P=1.46{\texttimes}10(-6)); 12q13.13 (rs4761974, P=8.71{\texttimes}10(-7)); 20p12.1 (rs6135309, P=3.69{\texttimes}10(-6)); and 4p15.31 (rs7664442, P=2.26{\texttimes}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.

}, keywords = {Adult, Aged, Cohort Studies, Disease Progression, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Leukoencephalopathies, Male, Middle Aged, Prospective Studies, White Matter}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.115.009252}, author = {Hofer, Edith and Cavalieri, Margherita and Bis, Joshua C and DeCarli, Charles and Fornage, Myriam and Sigurdsson, Sigurdur and Srikanth, Velandai and Trompet, Stella and Verhaaren, Benjamin F J and Wolf, Christiane and Yang, Qiong and Adams, Hieab H H and Amouyel, Philippe and Beiser, Alexa and Buckley, Brendan M and Callisaya, Michele and Chauhan, Ganesh and de Craen, Anton J M and Dufouil, Carole and van Duijn, Cornelia M and Ford, Ian and Freudenberger, Paul and Gottesman, Rebecca F and Gudnason, Vilmundur and Heiss, Gerardo and Hofman, Albert and Lumley, Thomas and Martinez, Oliver and Mazoyer, Bernard and Moran, Chris and Niessen, Wiro J and Phan, Thanh and Psaty, Bruce M and Satizabal, Claudia L and Sattar, Naveed and Schilling, Sabrina and Shibata, Dean K and Slagboom, P Eline and Smith, Albert and Stott, David J and Taylor, Kent D and Thomson, Russell and T{\"o}glhofer, Anna M and Tzourio, Christophe and van Buchem, Mark and Wang, Jing and Westendorp, Rudi G J and Windham, B Gwen and Vernooij, Meike W and Zijdenbos, Alex and Beare, Richard and Debette, Stephanie and Ikram, M Arfan and Jukema, J Wouter and Launer, Lenore J and Longstreth, W T and Mosley, Thomas H and Seshadri, Sudha and Schmidt, Helena and Schmidt, Reinhold} }