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Published on: August 15, 2019
Extreme evolutionary disparities seen in positive selection across seven complex diseases
Erik Corona1, Joel T Dudley, Atul J Butte
1Lucile Packard Children's Hospital, Stanford, California, United States of America.
Plos One
|September 3, 2010
Summary
Human evolution shows recent positive selection for disease susceptibility alleles in Type 1 Diabetes and Rheumatoid Arthritis, but not Crohn's Disease. This suggests complex diseases may arise from adaptations benefiting fitness.
Area of Science:
- Human evolutionary genetics
- Complex disease etiology
- Population genetics
Background:
- Genome-wide association studies (GWASs) identify disease-associated genetic variations.
- Human evolution and environmental changes may influence disease susceptibility.
- The role of positive selection in common complex diseases is not fully understood.
Purpose of the Study:
- To investigate evidence of recent positive selection in genes associated with seven common complex diseases.
- To determine if human evolution is trending towards or away from general disease susceptibility.
- To explore the potential trade-offs between increased fitness and disease susceptibility.
Main Methods:
- Analysis of single nucleotide polymorphisms (SNPs) from GWASs of seven diseases.
- Utilizing a comprehensive set of strongly associated SNPs to capture potential hidden associations.
- Applying statistical methods to detect signals of positive selection in the selected SNP sets.
Main Results:
- Evidence of recent positive selection was found for alleles associated with increased susceptibility to Type 1 Diabetes (T1D) and Rheumatoid Arthritis (RA).
- For T1D, selection favored susceptibility alleles over protective alleles (58 vs. 22 in top SNPs).
- Conversely, positive selection in Crohn's Disease (CD) associated SNPs favored protective alleles.
Conclusions:
- Recent positive selection may contribute to the genetic basis of certain complex diseases, potentially conferring fitness advantages.
- The direction of selection varies across diseases, with some favoring susceptibility (T1D, RA) and others protection (CD).
- These findings offer insights into disease origins and the identification of causal genetic factors.
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