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Updated: Feb 16, 2026

Genomic MRI - a Public Resource for Studying Sequence Patterns within Genomic DNA
Published on: May 9, 2011
Whole genome sequence analyses of brain imaging measures in the Framingham Study
Chloé Sarnowski1, Claudia L Satizabal2, Charles DeCarli2
1From the Department of Epidemiology (C.S., L.A.C., A.S.B., A.L.D., J.D.), Boston University School of Public Health; Boston University and the NHLBI's Framingham Heart Study (C.L.S., A.N.P., L.A.C., R.S.V., A.S.B., A.L.D., J.D., S.S.); Departments of Neurology (C.L.S., A.S.B., A.L.D., S.S.) and Cardiology, Preventive Medicine & Epidemiology (R.S.V.), Boston University School of Medicine, Boston, MA; Department of Neurology and Center for Neuroscience (C.D.), University of California at Davis; Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center, Jackson; Cardiovascular Health Research Unit (J.C.B.), Department of Medicine, University of Washington, Seattle; and Institute of Molecular Medicine (M.F.), University of Texas Health Science Center, Houston. chloesar@bu.edu.
Objective:
We sought to identify rare variants influencing brain imaging phenotypes in the Framingham Heart Study by performing whole genome sequence association analyses within the Trans-Omics for Precision Medicine Program.
Methods:
We performed association analyses of cerebral and hippocampal volumes and white matter hyperintensity (WMH) in up to 2,180 individuals by testing the association of rank-normalized residuals from mixed-effect linear regression models adjusted for sex, age, and total intracranial volume with individual variants while accounting for familial relatedness. We conducted gene-based tests for rare variants using (1) a sliding-window approach, (2) a selection of functional exonic variants, or (3) all variants.
Results:
We detected new loci in 1p21 for cerebral volume (minor allele frequency [MAF] 0.005, p = 10-8) and in 16q23 for hippocampal volume (MAF 0.05, p = 2.7 × 10-8). Previously identified associations in 12q24 for hippocampal volume (rs7294919, p = 4.4 × 10-4) and in 17q25 for WMH (rs7214628, p = 2.0 × 10-3) were confirmed. Gene-based tests detected associations (p ≤ 2.3 × 10-6) in new loci for cerebral (5q13, 8p12, 9q31, 13q12-q13, 15q24, 17q12, 19q13) and hippocampal volumes (2p12) and WMH (3q13, 4p15) including Alzheimer disease- (UNC5D) and Parkinson disease-associated genes (GBA). Pathway analyses evidenced enrichment of associated genes in immunity, inflammation, and Alzheimer disease and Parkinson disease pathways.
Conclusions:
Whole genome sequence-wide search reveals intriguing new loci associated with brain measures. Replication of novel loci is needed to confirm these findings.
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