Genome-wide Association Study for Vitamin D Levels Reveals 69 Independent Loci
| Autor: | Tom Dudding, Nicholas J. Timpson, Jian'an Luan, Ruth E. Mitchell, Vincenzo Forgetta, J. Brent Richards, Simon Haworth, Rupal L. Shah, Despoina Manousaki, Adil Harroud, Claudia Langenberg |
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| Přispěvatelé: | Shah, Rupal [0000-0001-8789-8869], Luan, Jian'an [0000-0003-3137-6337], Langenberg, Claudia [0000-0002-5017-7344], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Genome-wide association study Single-nucleotide polymorphism vitamin D Biology Genetic correlation Polymorphism Single Nucleotide Article 03 medical and health sciences 0302 clinical medicine Genetics Vitamin D and neurology SNP Humans Genetics (clinical) 2. Zero hunger rare variants Heritability genetic correlation gene-environment interaction pathway analysis Minor allele frequency 030104 developmental biology genome-wide association studies partitioned heritability Female 030217 neurology & neurosurgery Imputation (genetics) Genome-Wide Association Study |
| Zdroj: | Mitchell, R E, Dudding, T, Haworth, S, Timpson, N J, Manousaki, D, Harroud, A, Forgetta, V, Shah, R L, Luan, J, Langenberg, C & Richards, B 2020, ' Genome-wide Association Study for Vitamin D Levels Reveals 69 Independent Loci ', American Journal of Human Genetics, vol. 106, no. 3, pp. 327-337 . https://doi.org/10.1016/j.ajhg.2020.01.017 Am J Hum Genet |
| Popis: | We aimed to increase our understanding of the genetic determinants of vitamin D levels by undertaking a large-scale genome-wide as- sociation study (GWAS) of serum 25 hydroxyvitamin D (25OHD). To do so, we used imputed genotypes from 401,460 white British UK Biobank participants with available 25OHD levels, retaining single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) > 0.1% and imputation quality score > 0.3. We performed a linear mixed model GWAS on standardized log-transformed 25OHD, adjusting for age, sex, season of measurement, and vitamin D supplementation. These results were combined with those from a previous GWAS including 42,274 Europeans. In silico functional follow-up of the GWAS results was undertaken to identify enrich- ment in gene sets, pathways, and expression in tissues, and to investigate the partitioned heritability of 25OHD and its shared herita- bility with other traits. Using this approach, the SNP heritability of 25OHD was estimated to 16.1%. 138 conditionally independent SNPs were detected (p value < 6.6 3 109) among which 53 had MAF < 5%. Single variant association signals mapped to 69 distinct loci, among which 63 were previously unreported. We identified enrichment in hepatic and lipid metabolism gene pathways and enriched expression of the 25OHD genes in liver, skin, and gastrointestinal tissues. We observed partially shared heritability between 25OHD and socio-economic traits, a feature which may be mediated through time spent outdoors. Therefore, through a large 25OHD GWAS, we identified 63 loci that underline the contribution of genes outside the vitamin D canonical metabolic pathway to the genetic architec- ture of 25OHD. |
| Databáze: | OpenAIRE |
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