Replication study of chr17q25 with cerebral white matter lesion volume.

BACKGROUND AND PURPOSE Recently, the first genomewide association study on cerebral white matter lesion burden identified chr17q25 to be significantly associated with white matter lesions. We report on the first independent replication study of this genetic association. METHODS In a population-based cohort study, we investigated the association between the 6 genomewide significant single nucleotide polymorphisms at that locus and cerebral white matter lesion volume on MRI, measured quantitatively, adjusted for age, sex, and intracranial volume. Adjustments for ApoE4 carriership and cardiovascular risk factors were evaluated separately. Finally, we performed a meta-analysis of all published data for the single most significant single nucleotide polymorphism, rs3744028. RESULTS The risk alleles of all the 6 single nucleotide polymorphisms were significantly associated with white matter lesion volume with P=1.1*10(-3) for rs3744028, adjusted for age, sex, and intracranial volume. Additional adjustments only had minor influence on these associations. A meta-analysis with all published data for rs3744028 resulted in a probability value of 5.3*10(-17). CONCLUSIONS This study further establishes chr17q25 as a novel genetic locus for WML volume.