Structured sparse CCA for brain imaging genetics via graph OSCAR

BACKGROUND: Recently, structured sparse canonical correlation analysis (SCCA) has received increased attention in brain imaging genetics studies. It can identify bi-multivariate imaging genetic associations as well as select relevant features with desired structure information. These SCCA methods either use the fused lasso regularizer to induce the smoothness between ordered features, or use the signed pairwise difference which is dependent on the estimated sign of sample correlation. Besides, several other structured SCCA models use the group lasso or graph fused lasso to encourage group structure, but they require the structure/group information provided in advance which sometimes is not available. RESULTS: We propose a new structured SCCA model, which employs the graph OSCAR (GOSCAR) regularizer to encourage those highly correlated features to have similar or equal canonical weights. Our GOSCAR based SCCA has two advantages: 1) It does not require to pre-define the sign of the sample correlation, and thus could reduce the estimation bias. 2) It could pull those highly correlated features together no matter whether they are positively or negatively correlated. We evaluate our method using both synthetic data and real data. Using the 191 ROI measurements of amyloid imaging data, and 58 genetic markers within the APOE gene, our method identifies a strong association between APOE SNP rs429358 and the amyloid burden measure in the frontal region. In addition, the estimated canonical weights present a clear pattern which is preferable for further investigation. CONCLUSIONS: Our proposed method shows better or comparable performance on the synthetic data in terms of the estimated correlations and canonical loadings. It has successfully identified an important association between an Alzheimer’s disease risk SNP rs429358 and the amyloid burden measure in the frontal region.