Abstract
Obesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N = 761, 58% females, ages 18–81 years; 41.3 ± 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m2) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 × 1.7 × 3 mm; 55 directions). Additive genetic factors explained intersubject variance in BMI (heritability, h2 = 0.58), WC (h2 = 0.57), and FA (h2 = 0.49). FA shared significant portions of genetic variance with BMI in the genu (ρG = −0.25), body (ρG = −0.30), and splenium (ρG = −0.26) of the corpus callosum, internal capsule (ρG = −0.29), and thalamic radiation (ρG = −0.31) (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (ρG = −0.39, p = 0.020; ρG = −0.39, p = 0.030), which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors.
Highlights
Obesity is an immediate public health problem and the second leading cause of preventable death globally (Ogden et al, 2007)
We found that Body mass index (BMI) and waist circumference (WC) shared 6 and 2%, respectively, of genetic variation in global and up to 15% variation in region-specific fractional anisotropy values
The highest shared genetic variance was observed between fractional anisotropy and BMI/WC in the superior fronto-occipital fasciculus (15%) and between BMI in the internal capsule (8%), thalamic radiation (10%), and sub-regions of the corpus callosum
Summary
Obesity is an immediate public health problem and the second leading cause of preventable death globally (Ogden et al, 2007). Obesity is associated with white matter hyperintensities (Jagust et al, 2005) and neurochemical alterations (Gazdzinski et al, 2008), in addition to differences in white matter volumes (Jagust et al, 2005; Raji et al, 2010; Walther et al, 2010). Reduced white matter volumes have been reported in the frontal lobes, anterior cingulum, and corona radiata among obese older adults compared to lean participants (Raji et al, 2010; Walther et al, 2010). Findings of macrostructural white matter abnormalities in obesity are inconsistent, leading to investigations of microstructural architecture of white matter tracts using more sophisticated imaging modalities
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