Atlas of human diseases influenced by genetic variants with extreme allele frequency differences

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 1...

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Bibliographic Details
Published in:Human genetics 2017, Vol.136 (1), p.39-54
Main Authors: Sulovari, Arvis, Chen, Yolanda H., Hudziak, James J., Li, Dawei
Format: Article
Language:English
Subjects:
African Continental Ancestry Group - genetics
Analysis
Asian Continental Ancestry Group - genetics
Biomedical and Life Sciences
Biomedicine
Disease
European Continental Ancestry Group - genetics
Gene Frequency
Gene Function
Genes
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Genomes
Genomics
Health aspects
Human Genetics
Humans
Lactose
Linkage Disequilibrium
Metabolic Diseases
Models, Theoretical
Molecular Medicine
Original Investigation
Phenotype
Polymorphism, Single Nucleotide
Population genetics
Soil sciences
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Summary: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.
ISSN:0340-6717
1432-1203
DOI:10.1007/s00439-016-1734-y