ArticlePLoS genetics2015
Allelic Spectra of Risk SNPs Are Different for Environment/Lifestyle Dependent versus Independent Diseases.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Human NCR3 gene variants rs2736191 and rs11575837 alter longitudinal risk for development of pediatric malaria episodes and severe malarial anemia.BMC genomics · 2023Observational
- Exploring Lead loci shared between schizophrenia and Cardiometabolic traits.BMC genomics · 2022Article
- Genetic and in utero environmental contributions to DNA methylation variation in placenta.Human molecular genetics · 2021Article
- Immune System and Neuroinflammation in Idiopathic Parkinson's Disease: Association Analysis of Genetic Variants and miRNAs Interactions.Frontiers in genetics · 2021Article
- Genetic Determinants Highlight the Existence of Shared Etiopathogenetic Mechanisms Characterizing Age-Related Macular Degeneration and Neurodegenerative Disorders.Frontiers in neurology · 2021Article
- Association of Schizophrenia Risk With Disordered Niacin Metabolism in an Indian Genome-wide Association Study.JAMA psychiatry · 2019Article
- Phenotypic severity in a family with MEND syndrome is directly associated with the accumulation of potentially functional variants of cholesterol homeostasis genes.Molecular genetics & genomic medicine · 2019Article
- Genetic variability of five ADRB2 polymorphisms among Mexican Amerindian ethnicities and the Mestizo population.PloS one · 2019Article
- Are minor alleles more likely to be risk alleles?BMC medical genomics · 2018Article
- Empirical Bayes Estimation of Semi-parametric Hierarchical Mixture Models for Unbiased Characterization of Polygenic Disease Architectures.Frontiers in genetics · 2018Article
- Cardiology Meets Personalized Lifestyle Medicine.Integrative medicine (Encinitas, Calif.) · 2017Article
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Authors and funding
3 authors.
Funding
Abstract
Genome-wide association studies (GWAS) have generated sufficient data to assess the role of selection in shaping allelic diversity of disease-associated SNPs. Negative selection against disease risk variants is expected to reduce their frequencies making them overrepresented in the group of minor (<50%) alleles. Indeed, we found that the overall proportion of risk alleles was higher among alleles with frequency <50% (minor alleles) compared to that in the group of major alleles. We hypothesized that negative selection may have different effects on environment (or lifestyle)-dependent versus environment (or lifestyle)-independent diseases. We used an environment/lifestyle index (ELI) to assess influence of environmental/lifestyle factors on disease etiology. ELI was defined as the number of publications mentioning "environment" or "lifestyle" AND disease per 1,000 disease-mentioning publications. We found that the frequency distributions of the risk alleles for the diseases with strong environmental/lifestyle components follow the distribution expected under a selectively neutral model, while frequency distributions of the risk alleles for the diseases with weak environmental/lifestyle influences is shifted to the lower values indicating effects of negative selection. We hypothesized that previously selectively neutral variants become risk alleles when environment changes. The hypothesis of ancestrally neutral, currently disadvantageous risk-associated alleles predicts that the distribution of risk alleles for the environment/lifestyle dependent diseases will follow a neutral model since natural selection has not had enough time to influence allele frequencies. The results of our analysis suggest that prediction of SNP functionality based on the level of evolutionary conservation may not be useful for SNPs associated with environment/lifestyle dependent diseases.
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