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Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length
- Source :
- American Journal of Human Genetics, 106(3), 389-404. CELL PRESS, Li, C, Stoma, S, Lotta, L A, Warner, S, Albrecht, E, Allione, A, Arp, P P, Broer, L, Buxton, J L, Da Silva Couto Alves, A, Deelen, J, Fedko, I O, Gordon, S D, Jiang, T, Karlsson, R, Kerrison, N, Loe, T K, Mangino, M, Milaneschi, Y, Miraglio, B, Pervjakova, N, Russo, A, Surakka, I, van der Spek, A, Verhoeven, J E, Amin, N, Beekman, M, Blakemore, A I, Canzian, F, Hamby, S E, Hottenga, J-J, Jones, P D, Jousilahti, P, Mägi, R, Medland, S E, Montgomery, G W, Nyholt, D R, Perola, M, Pietiläinen, K H, Salomaa, V, Sillanpää, E, Suchiman, H E, van Heemst, D, Willemsen, G, Agudo, A, Boeing, H, Boomsma, D I, Chirlaque, M-D, Fagherazzi, G, Ferrari, P, Franks, P, Gieger, C, Eriksson, J G, Gunter, M, Hägg, S, Hovatta, I, Imaz, L, Kaprio, J, Kaaks, R, Key, T, Krogh, V, Martin, N G, Melander, O, Metspalu, A, Moreno, C, Onland-Moret, N C, Nilsson, P, Ong, K K, Overvad, K, Palli, D, Panico, S, Pedersen, N L, Penninx, B W J H, Quirós, J R, Jarvelin, M R, Rodríguez-Barranco, M, Scott, R A, Severi, G, Slagboom, P E, Spector, T D, Tjonneland, A, Trichopoulou, A, Tumino, R, Uitterlinden, A G, van der Schouw, Y T, van Duijn, C M, Weiderpass, E, Denchi, E L, Matullo, G, Butterworth, A S, Danesh, J, Samani, N J, Wareham, N J, Nelson, C P, Langenberg, C & Codd, V 2020, ' Genome-Wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length ', American Journal of Human Genetics, vol. 106, no. 3, pp. 389-404 . https://doi.org/10.1016/j.ajhg.2020.02.006, Am. J. Hum. Genet. 106, 389-404 (2020), American Journal of Human Genetics, 106(3), 389-404. Cell Press, Dipòsit Digital de la UB, Universidad de Barcelona, Am J Hum Genet, American journal of human genetics, 106(3), 389-404. Cell Press, American Journal of Human Genetics, Li, C, Stoma, S, Lotta, L A, Warner, S, Albrecht, E, Allione, A, Arp, P P, Broer, L, Buxton, J L, Da Silva Couto Alves, A, Deelen, J, Fedko, I O, Gordon, S D, Jiang, T, Karlsson, R, Kerrison, N, Loe, T K, Mangino, M, Milaneschi, Y, Miraglio, B, Pervjakova, N, Russo, A, Surakka, I, van der Spek, A, Verhoeven, J E, Amin, N, Beekman, M, Blakemore, A I, Canzian, F, Hamby, S E, Hottenga, J J, Jones, P D, Jousilahti, P, Mägi, R, Medland, S E, Montgomery, G W, Nyholt, D R, Perola, M, Pietiläinen, K H, Salomaa, V, Sillanpää, E, Suchiman, H E, van Heemst, D, Willemsen, G, Agudo, A, Boeing, H, Boomsma, D I, Chirlaque, M D, Fagherazzi, G, Ferrari, P, Franks, P, Gieger, C, Eriksson, J G, Gunter, M, Hägg, S, Hovatta, I, Imaz, L, Kaprio, J, Kaaks, R, Key, T, Krogh, V, Martin, N G, Melander, O, Metspalu, A, Moreno, C, Onland-Moret, N C, Nilsson, P, Ong, K K, Overvad, K, Palli, D, Panico, S, Pedersen, N L, Penninx, B W J H, Quirós, J R, Jarvelin, M R, Rodríguez-Barranco, M, Scott, R A, Severi, G, Slagboom, P E, Spector, T D, Tjonneland, A, Trichopoulou, A, Tumino, R, Uitterlinden, A G, van der Schouw, Y T, van Duijn, C M, Weiderpass, E, Denchi, E L, Matullo, G, Butterworth, A S, Danesh, J, Samani, N J, Wareham, N J, Nelson, C P, Langenberg, C & Codd, V 2020, ' Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length ', American journal of human genetics, vol. 106, no. 3, pp. 389-404 . https://doi.org/10.1016/j.ajhg.2020.02.006, American Journal of Human Genetics, 106(3), 389. Cell Press, Li, C, Stoma, S, Lotta, L A, Warner, S, Albrecht, E, Allione, A, Arp, P P, Broer, L, Buxton, J L, Da Silva Couto Alves, A, Deelen, J, Fedko, I O, Gordon, S D, Jiang, T, Karlsson, R, Kerrison, N, Loe, T K, Mangino, M, Milaneschi, Y, Miraglio, B, Pervjakova, N, Russo, A, Surakka, I, van der Spek, A, Verhoeven, J E, Amin, N, Beekman, M, Blakemore, A I, Canzian, F, Hamby, S E, Hottenga, J-J, Jones, P D, Jousilahti, P, Mägi, R, Medland, S E, Montgomery, G W, Nyholt, D R, Perola, M, Pietiläinen, K H, Salomaa, V, Sillanpää, E, Suchiman, H E, van Heemst, D, Willemsen, G, Agudo, A, Boeing, H, Boomsma, D I, Chirlaque, M-D, Fagherazzi, G, Ferrari, P, Franks, P, Gieger, C, Eriksson, J G, Gunter, M, Hägg, S, Hovatta, I, Imaz, L, Kaprio, J, Kaaks, R, Key, T, Krogh, V, Martin, N G, Melander, O, Metspalu, A, Moreno, C, Onland-Moret, N C, Nilsson, P, Ong, K K, Overvad, K, Palli, D, Panico, S, Pedersen, N L, Penninx, B W J H, Quirós, J R, Jarvelin, M R, Rodríguez-Barranco, M, Scott, R A, Severi, G, Slagboom, P E, Spector, T D, Tjonneland, A, Trichopoulou, A, Tumino, R, Uitterlinden, A G, van der Schouw, Y T, van Duijn, C M, Weiderpass, E, Denchi, E L, Matullo, G, Butterworth, A S, Danesh, J, Samani, N J, Wareham, N J, Nelson, C P, Langenberg, C & Codd, V 2020, ' Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length ', American Journal of Human Genetics, vol. 106, no. 3, pp. 389-404 . https://doi.org/10.1016/j.ajhg.2020.02.006
- Publication Year :
- 2020
- Publisher :
- Umeå universitet, Näringsforskning, 2020.
-
Abstract
- Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
- Subjects :
- Netherlands Twin Register (NTR)
Limfomes
LOCI
Genome-wide association study
Disease
VARIANTS
DISEASE
0302 clinical medicine
Leukocytes
telomere length
GWAS
Genetics(clinical)
Càncer
Mendelian randomisation
Thyroid cancer
Genetics (clinical)
11 Medical and Health Sciences
Cancer
Genetics
Genetics & Heredity
RISK
0303 health sciences
Telòmer
age-related disease
biological aging
Humans
Nucleotides
Genome-Wide Association Study
Telomere
meta-analyysi
genomiikka
Genomics
CANCER
3. Good health
030220 oncology & carcinogenesis
MENDELIAN RANDOMIZATION
Medical genetics
Biomarker (medicine)
HEART
Lymphomas
Life Sciences & Biomedicine
Medical Genetics
medicine.medical_specialty
GENES
DATABASE
Age-related Disease
Biological Aging
Mendelian Randomisation
Telomere Length
Biology
Article
03 medical and health sciences
SDG 3 - Good Health and Well-being
Mendelian randomization
medicine
Journal Article
030304 developmental biology
Medicinsk genetik
Science & Technology
06 Biological Sciences
medicine.disease
Genòmica
ikääntyminen
1182 Biochemistry, cell and molecular biology
telomeerit
biological
Subjects
Details
- Language :
- English
- ISSN :
- 00029297
- Database :
- OpenAIRE
- Journal :
- American Journal of Human Genetics, 106(3), 389-404. CELL PRESS, Li, C, Stoma, S, Lotta, L A, Warner, S, Albrecht, E, Allione, A, Arp, P P, Broer, L, Buxton, J L, Da Silva Couto Alves, A, Deelen, J, Fedko, I O, Gordon, S D, Jiang, T, Karlsson, R, Kerrison, N, Loe, T K, Mangino, M, Milaneschi, Y, Miraglio, B, Pervjakova, N, Russo, A, Surakka, I, van der Spek, A, Verhoeven, J E, Amin, N, Beekman, M, Blakemore, A I, Canzian, F, Hamby, S E, Hottenga, J-J, Jones, P D, Jousilahti, P, Mägi, R, Medland, S E, Montgomery, G W, Nyholt, D R, Perola, M, Pietiläinen, K H, Salomaa, V, Sillanpää, E, Suchiman, H E, van Heemst, D, Willemsen, G, Agudo, A, Boeing, H, Boomsma, D I, Chirlaque, M-D, Fagherazzi, G, Ferrari, P, Franks, P, Gieger, C, Eriksson, J G, Gunter, M, Hägg, S, Hovatta, I, Imaz, L, Kaprio, J, Kaaks, R, Key, T, Krogh, V, Martin, N G, Melander, O, Metspalu, A, Moreno, C, Onland-Moret, N C, Nilsson, P, Ong, K K, Overvad, K, Palli, D, Panico, S, Pedersen, N L, Penninx, B W J H, Quirós, J R, Jarvelin, M R, Rodríguez-Barranco, M, Scott, R A, Severi, G, Slagboom, P E, Spector, T D, Tjonneland, A, Trichopoulou, A, Tumino, R, Uitterlinden, A G, van der Schouw, Y T, van Duijn, C M, Weiderpass, E, Denchi, E L, Matullo, G, Butterworth, A S, Danesh, J, Samani, N J, Wareham, N J, Nelson, C P, Langenberg, C & Codd, V 2020, ' Genome-Wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length ', American Journal of Human Genetics, vol. 106, no. 3, pp. 389-404 . https://doi.org/10.1016/j.ajhg.2020.02.006, Am. J. Hum. Genet. 106, 389-404 (2020), American Journal of Human Genetics, 106(3), 389-404. Cell Press, Dipòsit Digital de la UB, Universidad de Barcelona, Am J Hum Genet, American journal of human genetics, 106(3), 389-404. Cell Press, American Journal of Human Genetics, Li, C, Stoma, S, Lotta, L A, Warner, S, Albrecht, E, Allione, A, Arp, P P, Broer, L, Buxton, J L, Da Silva Couto Alves, A, Deelen, J, Fedko, I O, Gordon, S D, Jiang, T, Karlsson, R, Kerrison, N, Loe, T K, Mangino, M, Milaneschi, Y, Miraglio, B, Pervjakova, N, Russo, A, Surakka, I, van der Spek, A, Verhoeven, J E, Amin, N, Beekman, M, Blakemore, A I, Canzian, F, Hamby, S E, Hottenga, J J, Jones, P D, Jousilahti, P, Mägi, R, Medland, S E, Montgomery, G W, Nyholt, D R, Perola, M, Pietiläinen, K H, Salomaa, V, Sillanpää, E, Suchiman, H E, van Heemst, D, Willemsen, G, Agudo, A, Boeing, H, Boomsma, D I, Chirlaque, M D, Fagherazzi, G, Ferrari, P, Franks, P, Gieger, C, Eriksson, J G, Gunter, M, Hägg, S, Hovatta, I, Imaz, L, Kaprio, J, Kaaks, R, Key, T, Krogh, V, Martin, N G, Melander, O, Metspalu, A, Moreno, C, Onland-Moret, N C, Nilsson, P, Ong, K K, Overvad, K, Palli, D, Panico, S, Pedersen, N L, Penninx, B W J H, Quirós, J R, Jarvelin, M R, Rodríguez-Barranco, M, Scott, R A, Severi, G, Slagboom, P E, Spector, T D, Tjonneland, A, Trichopoulou, A, Tumino, R, Uitterlinden, A G, van der Schouw, Y T, van Duijn, C M, Weiderpass, E, Denchi, E L, Matullo, G, Butterworth, A S, Danesh, J, Samani, N J, Wareham, N J, Nelson, C P, Langenberg, C & Codd, V 2020, ' Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length ', American journal of human genetics, vol. 106, no. 3, pp. 389-404 . https://doi.org/10.1016/j.ajhg.2020.02.006, American Journal of Human Genetics, 106(3), 389. Cell Press, Li, C, Stoma, S, Lotta, L A, Warner, S, Albrecht, E, Allione, A, Arp, P P, Broer, L, Buxton, J L, Da Silva Couto Alves, A, Deelen, J, Fedko, I O, Gordon, S D, Jiang, T, Karlsson, R, Kerrison, N, Loe, T K, Mangino, M, Milaneschi, Y, Miraglio, B, Pervjakova, N, Russo, A, Surakka, I, van der Spek, A, Verhoeven, J E, Amin, N, Beekman, M, Blakemore, A I, Canzian, F, Hamby, S E, Hottenga, J-J, Jones, P D, Jousilahti, P, Mägi, R, Medland, S E, Montgomery, G W, Nyholt, D R, Perola, M, Pietiläinen, K H, Salomaa, V, Sillanpää, E, Suchiman, H E, van Heemst, D, Willemsen, G, Agudo, A, Boeing, H, Boomsma, D I, Chirlaque, M-D, Fagherazzi, G, Ferrari, P, Franks, P, Gieger, C, Eriksson, J G, Gunter, M, Hägg, S, Hovatta, I, Imaz, L, Kaprio, J, Kaaks, R, Key, T, Krogh, V, Martin, N G, Melander, O, Metspalu, A, Moreno, C, Onland-Moret, N C, Nilsson, P, Ong, K K, Overvad, K, Palli, D, Panico, S, Pedersen, N L, Penninx, B W J H, Quirós, J R, Jarvelin, M R, Rodríguez-Barranco, M, Scott, R A, Severi, G, Slagboom, P E, Spector, T D, Tjonneland, A, Trichopoulou, A, Tumino, R, Uitterlinden, A G, van der Schouw, Y T, van Duijn, C M, Weiderpass, E, Denchi, E L, Matullo, G, Butterworth, A S, Danesh, J, Samani, N J, Wareham, N J, Nelson, C P, Langenberg, C & Codd, V 2020, ' Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length ', American Journal of Human Genetics, vol. 106, no. 3, pp. 389-404 . https://doi.org/10.1016/j.ajhg.2020.02.006
- Accession number :
- edsair.doi.dedup.....e238cacd13be676a0aea71ee6af24125
- Full Text :
- https://doi.org/10.1016/j.ajhg.2020.02.006