Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers
Almost all complex disorders have manifested epidemiological and clinical sex disparities which might partially arise from sex-specific genetic mechanisms. Addressing such differences can be important from a precision medicine perspective which aims to make medical interventions more personalized an...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/5/686 |
| _version_ | 1797535509953642496 |
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| author | Alireza Nazarian Alexander M. Kulminski |
| author_facet | Alireza Nazarian Alexander M. Kulminski |
| author_sort | Alireza Nazarian |
| collection | DOAJ |
| description | Almost all complex disorders have manifested epidemiological and clinical sex disparities which might partially arise from sex-specific genetic mechanisms. Addressing such differences can be important from a precision medicine perspective which aims to make medical interventions more personalized and effective. We investigated sex-specific genetic associations with colorectal (CRCa) and lung (LCa) cancers using genome-wide single-nucleotide polymorphisms (SNPs) data from three independent datasets. The genome-wide association analyses revealed that 33 SNPs were associated with CRCa/LCa at <i>P</i> < 5.0 × 10<sup>−6</sup> neither males or females. Of these, 26 SNPs had sex-specific effects as their effect sizes were statistically different between the two sexes at a Bonferroni-adjusted significance level of 0.0015. None had proxy SNPs within their ±1 Mb regions and the closest genes to 32 SNPs were not previously associated with the corresponding cancers. The pathway enrichment analyses demonstrated the associations of 35 pathways with CRCa or LCa which were mostly implicated in immune system responses, cell cycle, and chromosome stability. The significant pathways were mostly enriched in either males or females. Our findings provided novel insights into the potential sex-specific genetic heterogeneity of CRCa and LCa at SNP and pathway levels. |
| first_indexed | 2024-03-10T11:45:43Z |
| format | Article |
| id | doaj.art-e165cf84444f4371adbd4e2f02fecbb4 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T11:45:43Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-e165cf84444f4371adbd4e2f02fecbb42023-11-21T18:08:34ZengMDPI AGGenes2073-44252021-05-0112568610.3390/genes12050686Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal CancersAlireza Nazarian0Alexander M. Kulminski1Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC 27705, USABiodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC 27705, USAAlmost all complex disorders have manifested epidemiological and clinical sex disparities which might partially arise from sex-specific genetic mechanisms. Addressing such differences can be important from a precision medicine perspective which aims to make medical interventions more personalized and effective. We investigated sex-specific genetic associations with colorectal (CRCa) and lung (LCa) cancers using genome-wide single-nucleotide polymorphisms (SNPs) data from three independent datasets. The genome-wide association analyses revealed that 33 SNPs were associated with CRCa/LCa at <i>P</i> < 5.0 × 10<sup>−6</sup> neither males or females. Of these, 26 SNPs had sex-specific effects as their effect sizes were statistically different between the two sexes at a Bonferroni-adjusted significance level of 0.0015. None had proxy SNPs within their ±1 Mb regions and the closest genes to 32 SNPs were not previously associated with the corresponding cancers. The pathway enrichment analyses demonstrated the associations of 35 pathways with CRCa or LCa which were mostly implicated in immune system responses, cell cycle, and chromosome stability. The significant pathways were mostly enriched in either males or females. Our findings provided novel insights into the potential sex-specific genetic heterogeneity of CRCa and LCa at SNP and pathway levels.https://www.mdpi.com/2073-4425/12/5/686genetic heterogeneitysex-specific genetic polymorphismsGWASCRCaLCa |
| spellingShingle | Alireza Nazarian Alexander M. Kulminski Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers Genes genetic heterogeneity sex-specific genetic polymorphisms GWAS CRCa LCa |
| title | Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers |
| title_full | Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers |
| title_fullStr | Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers |
| title_full_unstemmed | Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers |
| title_short | Genome-Wide Analysis of Sex Disparities in the Genetic Architecture of Lung and Colorectal Cancers |
| title_sort | genome wide analysis of sex disparities in the genetic architecture of lung and colorectal cancers |
| topic | genetic heterogeneity sex-specific genetic polymorphisms GWAS CRCa LCa |
| url | https://www.mdpi.com/2073-4425/12/5/686 |
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