Scoring the collective effects of SNPs: association of minor alleles with complex traits in model organisms
| Autor: | Xiaohua Tan, Dapeng Wang, Zuobin Zhu, Shi Huang, Xian Man, Ayca Dogan, Oliver Goldmann, Hui Guo, Qing Lu, Yanke Li, Yimin Huang, Amanda D. Rice, Jie Liang, Eva Medina, Kun Xia, Dejian Yuan, Long Ma, Jiegen Zhang, Ceng Zeng, Ke Yi, Jun Chen, Jun Yu, Gudrun A. Brockmann, Richard W. Moyer |
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| Rok vydání: | 2014 |
| Předmět: |
Genetics
0303 health sciences Agricultural and Biological Sciences(all) Nematoda Biochemistry Genetics and Molecular Biology(all) Genome-wide association study Single-nucleotide polymorphism Disease Biology Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Negative selection 0302 clinical medicine Environmental Science(all) Missing heritability problem Trait Animals Allele Stabilizing selection General Agricultural and Biological Sciences Alleles 030217 neurology & neurosurgery 030304 developmental biology General Environmental Science |
| Zdroj: | Science China Life Sciences. 57:876-888 |
| ISSN: | 1869-1889 1674-7305 |
| DOI: | 10.1007/s11427-014-4704-4 |
| Popis: | Most common SNPs are popularly assumed to be neutral. We here developed novel methods to examine in animal models and humans whether extreme amount of minor alleles (MAs) carried by an individual may represent extreme trait values and common diseases. We analyzed panels of genetic reference populations and identified the MAs in each panel and the MA content (MAC) that each strain carried. We also analyzed 21 published GWAS datasets of human diseases and identified the MAC of each case or control. MAC was nearly linearly linked to quantitative variations in numerous traits in model organisms, including life span, tumor susceptibility, learning and memory, sensitivity to alcohol and anti-psychotic drugs, and two correlated traits poor reproductive fitness and strong immunity. Similarly, in Europeans or European Americans, enrichment of MAs of fast but not slow evolutionary rate was linked to autoimmune and numerous other diseases, including type 2 diabetes, Parkinson's disease, psychiatric disorders, alcohol and cocaine addictions, cancer, and less life span. Therefore, both high and low MAC correlated with extreme values in many traits, indicating stabilizing selection on most MAs. The methods here are broadly applicable and may help solve the missing heritability problem in complex traits and diseases. |
| Databáze: | OpenAIRE |
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