title: Atlas of human diseases influenced by genetic variants with extreme allele frequency differences.
abstract: Genetic variants with extreme allele frequency differences (EAFD) may underlie some human health disparities across populations. To identify EAFD loci, we systematically analyzed and characterized 81 million genomic variants from 2504 unrelated individuals of 26 world populations (phase III of the 1000 Genomes Project). Our analyses revealed a total of 434 genes, 15 pathways, and 18 diseases and traits influenced by EAFD variants from five continental populations. They included known EAFD genes, such as LCT (lactose tolerance), SLC24A5 (skin pigmentation), and EDAR (hair morphology). We found many novel EAFD genes, including TBC1D2B (autophagy mediator), TRIM40 (gastrointestinal inflammatory regulator), KRT71, KRT75, KRT83, and KRTAP10-1 (hair and epithelial keratin synthesis), PIK3R3 (insulin receptor interaction), DARS (neurological disorders), and NACA2 (skin inflammatory response). Our results also showed four complex diseases significantly associated with EAFD loci, including asthma (adjusted enrichment P = 4 × 10-8), type I diabetes (P = 6 × 10-9), alcohol consumption (P = 0.0002), and attention deficit/hyperactivity disorder (P = 0.003). This study provides a comprehensive atlas of genes, pathways, and human diseases significantly influenced by EAFD variants.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT, 05405, USA.
authors.forename: Arvis
authors.initials: A
authors.lastname: Sulovari
authors.affiliation: Department of Plant and Soil Science, University of Vermont, Burlington, VT, 05405, USA.
authors.forename: Yolanda H
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Vermont Center for Children, Youth, and Families, Department of Psychiatry, University of Vermont, Burlington, VT, 05405, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Hudziak
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT, 05405, USA. dawei.li@uvm.edu.|Department of Computer Science, University of Vermont, Burlington, VT, 05405, USA. dawei.li@uvm.edu.|Neuroscience, Behavior, and Health Initiative, University of Vermont, Burlington, VT, 05405, USA. dawei.li@uvm.edu.
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
mesh_terms: D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008962:Models, Theoretical; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics