Genome-wide scan for white matter hyperintensity: the Framingham Heart Study

Area of Science:

• Neurogenetics
• Medical Imaging
• Population Genetics

Background:

• White matter hyperintensity (WMH) volume is linked to aging and cerebrovascular disease.
• WMH exhibits high heritability, as observed in the Framingham Heart Study.
• Identifying genetic factors influencing WMH is crucial for understanding these conditions.

Purpose of the Study:

• To conduct a genome-wide linkage analysis to pinpoint chromosomal regions associated with WMH volume.
• To investigate the genetic underpinnings of WMH in a family-based cohort.

Main Methods:

• Brain MRI scans were used to quantify WMH and total cranial volume (TCV) in 2259 participants.
• Age-specific z-scores of the WMH to TCV ratio were calculated for linkage analysis.
• Variance component linkage analysis was performed on 747 individuals from 237 families with genetic and imaging data.

Main Results:

• Significant evidence of linkage (LOD score=3.69) was found on chromosome 4 at 4 cM.
• A suggestive linkage peak (LOD score=1.78) was identified on chromosome 17 at 95 cM.

Conclusions:

• A gene influencing WMH volume is significantly located on chromosome 4.
• This finding provides a genetic locus for further investigation into WMH.