A systematic SNP selection approach to identify mechanisms underlying disease aetiology: linking height to post-menopausal breast and colorectal cancer risk
| Autor: | Aaron Isaacs, Colinda C. J. M. Simons, Bas A.J. Verhage, Piet A. van den Brandt, Mona Riemenschneider, Matty P. Weijenberg, Roger W. L. Godschalk, Kristel Van Steen, Rachel J. J. Elands, Monika Stoll, Leo J. Schouten |
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| Přispěvatelé: | Epidemiology, Epidemiologie, RS: GROW - R1 - Prevention, Promovendi ODB, Biochemie, RS: FHML MaCSBio, RS: CARIM - R1.01 - Blood proteins & engineering, Farmacologie en Toxicologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, RS: NUTRIM - R4 - Gene-environment interaction, RS: CAPHRI - R5 - Optimising Patient Care |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
GROWTH-PLATE MELANIN-CONCENTRATING HORMONE Single-nucleotide polymorphism Genome-wide association study Breast Neoplasms Biology Polymorphism Single Nucleotide BETA-SIGNALING PATHWAY Article MAMMARY-GLAND DEVELOPMENT 03 medical and health sciences SDG 3 - Good Health and Well-being Genetic linkage Mendelian randomization medicine SNP Humans Genetic Predisposition to Disease International HapMap Project Risk factor GENOME-WIDE ASSOCIATION RECTAL-CANCER Genetics Multidisciplinary ANDROGEN RECEPTOR Cancer TGF-BETA medicine.disease GENE-ENVIRONMENT INTERACTIONS Body Height Postmenopause 030104 developmental biology MENDELIAN RANDOMIZATION Female Colorectal Neoplasms Genome-Wide Association Study |
| Zdroj: | Scientific Reports Scientific Reports, 7:41034. Nature Publishing Group |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep41034 |
| Popis: | Data from GWAS suggest that SNPs associated with complex diseases or traits tend to co-segregate in regions of low recombination, harbouring functionally linked gene clusters. This phenomenon allows for selecting a limited number of SNPs from GWAS repositories for large-scale studies investigating shared mechanisms between diseases. For example, we were interested in shared mechanisms between adult-attained height and post-menopausal breast cancer (BC) and colorectal cancer (CRC) risk, because height is a risk factor for these cancers, though likely not a causal factor. Using SNPs from public GWAS repositories at p-values −5 and a genomic sliding window of 1 mega base pair, we identified SNP clusters including at least one SNP associated with height and one SNP associated with either post-menopausal BC or CRC risk (or both). SNPs were annotated to genes using HapMap and GRAIL and analysed for significantly overrepresented pathways using ConsensuspathDB. Twelve clusters including 56 SNPs annotated to 26 genes were prioritised because these included at least one height- and one BC risk- or CRC risk-associated SNP annotated to the same gene. Annotated genes were involved in Indian hedgehog signalling (p-value = 7.78 × 10−7) and several cancer site-specific pathways. This systematic approach identified a limited number of clustered SNPs, which pinpoint potential shared mechanisms linking together the complex phenotypes height, post-menopausal BC and CRC. |
| Databáze: | OpenAIRE |
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