Sharing of Genes and Pathways Across Complex Phenotypes: A Multilevel Genome-Wide Analysis

Genetics
Hongsheng GuiMiaoxin Li

Abstract

Evidence from genome-wide association studies (GWAS) suggest that pleiotropic effects on human complex phenotypes are very common. Recently, an atlas of genetic correlations among complex phenotypes has broadened our understanding of human diseases and traits. Here, we examine genetic overlap, from a gene-centric perspective, among the same 24 phenotypes previously investigated for genetic correlations. After adopting the multilevel pipeline (freely available at http://grass.cgs.hku.hk/limx/kgg/), which includes intragenic single nucleotide polymorphisms (SNPs), genes, and gene-sets, to estimate genetic similarities across phenotypes, a large amount of sharing of several biologically related phenotypes was confirmed. In addition, significant genetic overlaps were also found among phenotype pairs that were previously unidentified by SNP-level approaches. All these pairs with new genetic links are supported by earlier epidemiological evidence, although only a few of them have pleiotropic genes in the GWAS Catalog. Hence, our gene and gene-set analyses are able to provide new insights into cross-phenotype connections. The investigation on genetic sharing at three different levels presents a complementary picture of how common DNA ...Continue Reading

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Nov 19, 2017·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Hongsheng GuiStacey S Cherny
Jul 15, 2020·Translational Psychiatry·Marcela Henriquez-HenriquezMaximilian Muenke

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