Association of relative brain age with tobacco smoking, alcohol consumption, and genetic variants

Abstract

Brain age is a metric that quantifies the degree of aging of a brain based on whole-brain anatomical characteristics. While associations between individual human brain regions and environmental or genetic factors have been investigated, how brain age is associated with those factors remains unclear. We investigated these associations using UK Biobank data. We first trained a statistical model for obtaining relative brain age (RBA), a metric describing a subject's brain age relative to peers, based on whole-brain anatomical measurements, from training set subjects (n = 5,193). We then applied this model to evaluation set subjects (n = 12,115) and tested the association of RBA with tobacco smoking, alcohol consumption, and genetic variants. We found that daily or almost daily consumption of tobacco and alcohol were both significantly associated with increased RBA (P < 0.001). We also found SNPs significantly associated with RBA (p-value < 5E-8). The SNP most significantly associated with RBA is located in MAPT gene. Our results suggest that both environmental and genetic factors are associated with structural brain aging.

Figure 1

Procedure for studying the association of relative brain age with smoking, alcohol consumption, and genetic variation.

Figure 2

Relationship between chronological age and the predicted brain age. Subjects with positive relative brain age (RBA) are labeled with blue X’s; subjects with negative RBA are labeled with red dots. The RBA of a specific subject is illustrated in pink color.

Figure 3

Relationship between Fluid intelligence score and relative brain age (RBA). Subjects with Fluid score of 0, 1, 2, and 3 (n = 28, 114, and 361, respectively) are grouped together. Subjects with Fluid score of 11, 12, and 13 (n = 334, 111, and 17, respectively) are grouped together, so that each group has more than 200 subjects.

Figure 4

Relationship between previous tobacco smoking frequency and relative brain age.

Figure 5

Relationship between alcohol intake frequency and relative brain age.

Figure 6

Manhattan plot for the association p-values between genetic variants and relative brain age across the genome. The red line indicates the genome-wide significant threshold on p-value (i.e., 5E-8). The blue line indicates p-value of 0.05.