Abstract
Machine learning algorithms can be trained to estimate age from brain structural MRI. The difference between an individual's predicted and chronological age, predicted age difference (PAD), is a phenotype of relevance to aging and brain disease. Here, we present a new deep learning approach to predict brain age from a T1-weighted MRI. The method was trained on a dataset of healthy Icelanders and tested on two datasets, IXI and UK Biobank, utilizing transfer learning to improve accuracy on new sites. A genome-wide association study (GWAS) of PAD in the UK Biobank data (discovery set: N=12378$$N=12378$$, replication set: N=4456$$N=4456$$) yielded two sequence variants, rs1452628-T (β=−0.08$$\beta =-0.08$$, P=1.15×10−9$$P=1.15\times{10}^{-9}$$) and rs2435204-G (β=0.102$$\beta =0.102$$, P=9.73×10−12$$P=9.73\times 1{0}^{-12}$$). The former is near KCNK2 and correlates with reduced sulcal width, whereas the latter correlates with reduced white matter surface area and tags a well-known inversion at 17q21.31 (H2).</p>