Sai Zhang, Johnathan Cooper-Knock, Annika K Weimer, Minyi Shi, Tobias Moll, Jack N G Marshall, Calum Harvey, Helia Ghahremani Nezhad, John Franklin, Cleide Dos Santos Souza, Ke Ning, Cheng Wang, Jingjing Li, Allison A Dilliott, Sali Farhan, Eran Elhaik, Iris Pasniceanu, Matthew R Livesey, Chen Eitan, Eran Hornstein, Kevin P Kenna, Jan H Veldink, Laura Ferraiuolo, Pamela J Shaw, Michael P Snyder
Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed a machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. With transcriptomic and epigenetic profiling of motor neurons derived from induced pluripotent stem cells (iPSCs), RefMap identified 690 ALS-associated genes that represent a 5-fold increase in recovered heritability...
March 16, 2022: Neuron