Authors
Kuaikuai Duan, Jiayu Chen, Vince D Calhoun, Wenhao Jiang, Kelly Rootes-Murdy, Gido Schoenmacker, Rogers F Silva, Barbara Franke, Jan K Buitelaar, Martine Hoogman, Jaap Oosterlaan, Pieter J Hoekstra, Dirk Heslenfeld, Catharina A Hartman, Emma Sprooten, Alejandro Arias-Vasquez, Jessica A Turner, Jingyu Liu
Publication date
2020/7/12
Journal
bioRxiv
Pages
2020.07. 11.198622
Publisher
Cold Spring Harbor Laboratory
Description
Most psychiatric disorders are highly heritable and associated with altered brain structural and functional patterns. Data fusion analyses on brain imaging and genetics, one of which is parallel independent component analysis (pICA), enable the link of genomic factors to brain patterns. Due to the small to modest effect sizes of common genetic variants in psychiatric disorders, it is usually challenging to reliably separate disorder-related genetic factors from the rest of the genome with the typical size of clinical samples. To alleviate this problem, we propose sparse parallel independent component analysis (spICA) to leverage the sparsity of individual genomic sources. The sparsity is enforced by performing Hoyer projection on the estimated independent sources. Simulation results demonstrate that the proposed spICA yields improved detection of independent sources and imaging-genomic associations compared to pICA. We applied spICA to gray matter volume (GMV) and single nucleotide polymorphism (SNP) data of 341 unrelated adults, including 127 controls, 167 attention-deficit/hyperactivity disorder (ADHD) cases, and 47 unaffected siblings. We identified one SNP source significantly and positively associated with a GMV source in superior/middle frontal regions. This association was replicated with a smaller effect size in 317 adolescents from ADHD families, including 188 individuals with ADHD and 129 unaffected siblings. The association was found to be more significant in ADHD families than controls, and stronger in adults and older adolescents than younger ones. The identified GMV source in superior/middle frontal regions was not …
Total citations
2021202232