Background and Purpose White matter lesion (WML) progression on magnetic resonance imaging (MRI) is related to cognitive decline and Lomitapide stroke but its determinants besides baseline WML burden are largely unknown. 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 seven cohorts risk models including demographics vascular risk factors plus single nucleotide polymorphisms (SNPs) 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 SNPs achieved genome-wide significance (p-value < 5×10?8). Four loci were suggestive (p-value < 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 described just 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 life-style or host-related biological factors. and TRIM47) the WW domain binding protein 2 Lomitapide gene (WBP2) the mitochondrial ribosomal protein L38 gene (MRPL38) the Fas-binding factor 1 gene (FBF1) the acyl-coenzyme A oxidase 1 gene (ACOX1) and the C-Elegans Lomitapide homolog (UNC13D) gene. Although genetic factors may play an important role in the occurrence of WML in middle-aged to older adults whether these genes or others influence the further progression of WML is unknown. Using data on WML progression from all the cohorts currently available within the CHARGE consortium we examined the heritability of WML progression and performed a meta-analysis of GWAS data in 7773 individuals of European descent from 10 cohorts to identify common single nucleotide polymorphisms (SNPs) that influence the risk for WML progression. We also assessed the relative contribution of genetic factors in predicting WML progression beyond information that can be obtained from baseline clinical and MRI data alone. Materials and Methods Study Population Study participants were from 10 prospective cohort studies collaborating in the CHARGE Consortium8: the Aging Gene-Environment Susceptibility Reykjavik Study (AGES-Reykjavik)13 Smad7 the Atherosclerosis Risk in Communities (ARIC) study14 the Austrian Stroke Prevention Study (ASPS)15 16 the Cardiovascular Health Study (CHS)17 the Framingham Heart Study (FHS)18 19 the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)20 21 the Rotterdam Study II (RS II ) and the Rotterdam Study III (RS III)22 the Tasmanian Study of Cognition and Gait (TASCOG)23 and the 3C-Dijon study.24 All participating studies agreed on phenotype harmonization covariate selection pre-specified analytic plans for within-study analyses and meta-analysis of results. Each research secured authorization from Institutional Review Planks and all individuals provided written educated consent for research participation MRI checking and usage of DNA for hereditary research. Participants had been eligible for the existing research if they got genotyping serial MRI and lacked a brief history of transient ischemic episodes strokes dementia or any mix of these circumstances. All the people in today’s analysis had been whites of Western descent. Lomitapide The amount of individuals and their features in each cohort are demonstrated in Supplemental Desk I in the online-only Data Health supplement. WML Progression Evaluation In each research eligible individuals were invited to endure serial MRI scans that have been performed and interpreted inside a standardized style without understanding of demographic medical or hereditary info (Section II in the online-only Data Health supplement). Aside from ARIC and CHS whose visitors utilized a 10-stage scale visitors in the Lomitapide additional cohorts measured the quantity of WML on each MRI scan. WML development was thought as absent or present (Section.