The human brain's network architecture is genetically encoded by modular pleiotropy

Abstract

For much of biology, the manner in which genotype maps to phenotype remains a fundamental mystery. The few maps that are known tend to show modular pleiotropy: sets of phenotypes are determined by distinct sets of genes. One key map that has evaded discovery is that of the human brain's network architecture. Here, we determine the form of this map for gene coexpression and single nucleotide polymorphisms. We discover that mostly non-overlapping sets of genes encode the connectivity of brain network modules (or so-called communities), suggesting that brain network communities demarcate genetic transitions. We find that these clean boundaries break down at connector hubs, whose integrative connectivity is encoded by pleiotropic genes from mostly non-overlapping sets. Broadly, this study opens fundamentally new directions in the study of genetic encoding of brain development, evolution, and disease.