Genetics of age-related white matter lesions from linkage to genome wide association studies.

White matter lesions are a frequent phenomenon in the elderly and contribute to the development of disability. The mechanisms underlying these brain lesions are still not fully understood with age and hypertension being the most well established risk factors. The heritability of white matter lesions is consistently high in different populations. Candidate gene studies strongly support the role of genes involved in the renin-angiotensin system, as well as Notch3 signaling. The recent genome wide association study by the CHARGE consortium identified a novel locus on chromosome 17q25 harboring several genes such as TRIM65 and TRIM47 which pinpoint to possible novel mechanisms leading to white matter lesions.