title: Evidence of Polygenic Adaptation in the Systems Genetics of Anthropometric Traits.
abstract: Many signals of natural selection have been identified in the human genome. However, except for some single-locus mechanisms, most molecular processes generating these adaptation signals are still unknown. We developed an approach that integrates datasets related to genome-wide association studies (GWAS) with information about systems biology and genetic signatures of natural selection to identify evidence of polygenic adaptation. Specifically, we focused on five anthropometric measurements: body mass index (BMI), height, waist-to-hip ratio adjusted for BMI (WHR), and waist circumference adjusted for BMI (WC), and sex differences for WHR and WC. We performed an enrichment analysis for signals of natural selection in protein interaction networks associated with anthropometric traits in European populations. The adaptation signals-enriched gene networks associated highlighted epistatic interactions in the context of polygenic selection for the investigated traits. These polygenic mechanisms indicated intriguing selective mechanisms related to the anthropometric traits: adult locomotory behavior for BMI, infection resistance for height, interplay between lipid transport and immune systems for WHR, and female-specific polygenic adaptation for WHR and WC. In conclusion, we observed evidence of polygenic adaptation in the context of systems genetics of anthropometric traits that indicates polygenic mechanisms related to the natural selection in European populations.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, West Haven, Connecticut, United States of America.|VA CT Healthcare Center, West Haven, Connecticut, United States of America.
authors.forename: Renato
authors.initials: R
authors.lastname: Polimanti
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, West Haven, Connecticut, United States of America.|VA CT Healthcare Center, West Haven, Connecticut, United States of America.
authors.forename: Bao Zhu
authors.initials: BZ
authors.lastname: Yang
authors.affiliation: Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut, United States of America.|Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, West Haven, Connecticut, United States of America.|VA CT Healthcare Center, West Haven, Connecticut, United States of America.|Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States of America.|Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
mesh_terms: D000222:Adaptation, Physiological; D000886:Anthropometry; D015992:Body Mass Index; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020412:Multifactorial Inheritance; D060066:Protein Interaction Maps; D012641:Selection, Genetic; D012727:Sex Characteristics; D049490:Systems Biology; D055105:Waist Circumference; D049629:Waist-Hip Ratio