A Genome Wide Association Study for Longevity in Cattle


Longevity is regarded as the most important functional trait in cattle breeding with high economic value yet low heritability. In order to identify genomic regions associated with longevity, a genome wise association study was performed using data from 4887 Fleckvieh bulls and 33,556 SNPs after quality control. Single SNP regression was used for identification of important SNPs including eigenvectors as a means of correction for population structure. SNPs selected with a false discovery rate threshold of 0.05 and with local false discovery rate identified genomic regions associated with longevity which were subsequently cross checked with the National Center for Biotechnology Information (NCBI) database. This, to identify interesting genes in cattle and their homologue forms in other species. The most notable genes were SYT10 located on chromosome 5, ADAMTS3 on chromosome 6, NTRK2 on chromosome 8 and SNTG1 on chromosome 14 of the cattle genome. Several of the genes found have previously been associated with cattle fertility. Poor fertility is an important culling reason and thereby affects longevity in cattle. Several signals were located in regions sparse with described genes, which suggest that there might be several other non-identified genetic pathways for this important trait.

Share and Cite:

Mészáros, G. , Eaglen, S. , Waldmann, P. and Sölkner, J. (2014) A Genome Wide Association Study for Longevity in Cattle. Open Journal of Genetics, 4, 46-55. doi: 10.4236/ojgen.2014.41007.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Pritchard, T., Coffey, M., Mrode, R. and Wall, E. (2013) Understanding the Genetics of Survival in Dairy Cows. Journal of Dairy Science, 96, 3296-3309. http://dx.doi.org/10.3168/jds.2012-6219
[2] Essl, A. (1998) Longevity in Dairy Cattle Breeding: A Review. Livestock Production Science, 57, 79-89.
[3] Vukasovic, N., Moll, J. and Casanova, L. (2001) Implementation of Routine Genetic Evaluation for Longevity Based on Survival Analysis Techniques in Dairy Cattle Populations in Switzerland. Journal of Dairy Science, 84, 2073-2080.
[4] Egger-Danner, Ch., Kadlecík, O., Fuerst, C. and Kasarda, R. (2005) Joint Genetic Evaluation for Functional Longevity for Pinzgau Cattle. Book of abstracts of the 56th Annual Meeting of the European Association for Animal Production, Uppsala, 5-8 June 2005, 54.
[5] Van der Linde, C., de Jong, G., Simai, Sz., Gombacsi, P. and Wellisch, P. (2006) Genetic Evaluation for Longevity in Hungary. Interbull Bulletin, 35, 3-8.
[6] Mészáros, G., Pálos, J., Ducrocq, V. and Sölkner, J. (2010) Heritability of Longevity in Large White and Landrace Sows Using Continuous Time and Grouped Data Models. Genetics, Selection, Evolution, 42, 13.
[7] Kenyon, C., Chang, J., Gensch, E., Rudner, A. and Tabtiang, R. (1993) C. elegans Mutant That Lives Twice as Long as Wild Type. Nature, 366, 461-464. http://dx.doi.org/10.1038/366461a0
[8] Kimura, K.D., Tissenbaum, H.A., Liu, Y. and Ruvkun, G. (1997) daf-2, an Insulin Receptor-Like Gene That Regulates Longevity and Diapause in Caenorhabditiselegans. Science, 277, 942-946.
[9] Gami, M.S. and Wolkow, C.A. (2006) Studies of Caenorhabditiselegans DAF-2/Insulin Signaling Reveal Targets for Pharmacological Manipulation of Life Span. Aging Cell, 5, 31-37.
[10] Kenyon, C. (2005) The Plasticity of Aging: Insights from Long-Lived Mutants. Cell, 120, 449-460.
[11] Bartke, A. (2009) Insulin and Aging. Cell Cycle, 7, 3338-3343. http://dx.doi.org/10.4161/cc.7.21.7012
[12] Kenyon, C. (2010) The Genetics of Aging. Nature, 464, 504-512. http://dx.doi.org/10.1038/nature08980
[13] Garcia, M.D., Michal, J., Gaskins, C.T., Reeves, J.J., Ott, T.L., Liu, Y. and Jiang, Z. (2006) Significant Association of the Calpastatin Gene with Fertility and Longevity in Dairy Cattle. Animal Genetics, 37, 304-305.
[14] Weller, J.I., Golik, M., Reikhav, S., Domochovsky, R., Seroussi, E. and Ron, M. (2008) Detection and Analysis of Quantitative Trait Loci Affecting Production and Secondary Traits on Chromosome 7 in Israeli Holsteins. Journal of Dairy Science, 91, 802-813. http://dx.doi.org/10.3168/jds.2007-0367
[15] Wang, X., Maltecca, C., Tal-Stein, R., Lipkin, E. and Khatib, H. (2008) Association of Bovine Fibroblast Growth Factor 2 (FGF2) Gene with Milk Fat and Productive Life: An Example of the Ability of the Candidate Pathway Strategy to Identify Quantitative Trait Genes. Journal of Dairy Science, 91, 2475-2480.
[16] Khatib, H., Schutzkus, V., Chang, Y.M. and Rosa, G.J.M. (2007) Pattern of Expression of the Uterine Milk Protein Gene and Its Association with Productive Life in Dairy Cattle. Journal of Dairy Science, 90, 2427-2433.
[17] Szyda, J., Morek-Kopec, M., Komisarek, J. and Zarnecki, A. (2011) Evaluating Markers in Selected Genes for Association with Functional Longevity of Dairy Cattle. BMC Genetics, 12, 30.
[18] Fadista, J. and Bendixen, C. (2012) Genomic Position Mapping Discrepancies of Commercial SNP chips. PLoS One, 7, Article ID: e31025. http://dx.doi.org/10.1371/journal.pone.0031025
[19] Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A.R., Bender, D., Maller, J., Sklar, P., de Bakker, P.I.W., Daly, M.J. and Sham, P.C. (2007) PLINK: A Toolset for Whole-Genome Association and Population-Based Linkage Analysis. American Journal of Human Genetics, 81, 559-575. http://dx.doi.org/10.1086/519795
[20] Garrick, D.J., Taylor, J.F. and Fernando, R.L. (2009) Deregressing Estimated Breeding Values and Weighting Information for Genomic Regression Analyses. Genetics, Selection, Evolution, 41, 55.
[21] R Core Team (2012) R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna. http://www.R-project.org/
[22] Klei, L., Kent, B.P., Melhem, N., Devlin, B. and Roeder, K. (2011) GemTools: A Fast and Efficient Approach to Estimating Genetic Ancestry. http://arxiv.org/abs/1104.1162
[23] Lee, A., Luca, D., Klei, L., Devlin, B. and Roeder, K. (2010) Discovering Genetic Ancestry Using Spectral Graph Theory. Genetic Epidemiology, 34, 51-59.
[24] Price, A.L., Patterson, N.J., Plenge, R.M., Weinblatt, M.E., Shadick, N.A. and Reich, D. (2006) Principal Components Analysis Corrects for Stratification in Genome-Wide Association Studies. Nature Genetics, 38, 904-909.
[25] Benjamini, Y. and Hochberg, Y. (1995) Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society, Series B, 57, 289-300.
[26] Storey, J.D. and Tibshirani, R. (2003) Statistical Significance for Genomewide Studies. Proceedings of the National Academy of Sciences of the United States of America, 100, 9440-9445.
[27] Storey, J.D. (2002) A Direct Approach to False Discovery Rates. Journal of the Royal Statistical Society: Series B, 64, 479-498. http://dx.doi.org/10.1111/1467-9868.00346
[28] Efron, B. (2010) Large-Scale Inference Empirical Bayes Methods for Estimation, Testing, and Prediction. Cambridge Press, Cambridge. http://dx.doi.org/10.1017/CBO9780511761362
[29] Efron, B., Turnbull, B.B. and Narasimhan, B. (2011) Locfdr: Computes Local False Discovery Rates. R package version 1.1-7. http://CRAN.R-project.org/package=locfdr
[30] Ndiaye, K., Lussier, J.G. and Pate, J.L. (2010) Molecular Characterization and Expression of DERL1 in Bovine Ovarian Follicles and Corpora Lutea. Reproductive Biology and Endocrinology, 8, 94.
[31] Wilk, J.B., Walter, R.E., Laramie, J.M., Gottlieb, D.J. and O’Connor, G.T. (2007) Framingham Heart Study Genome-Wide Association: Results for Pulmonary Function Measures. BMC Medical Genetics, 19, S8.
[32] Bashiardes, S., Veile, R., Allen, M., Wise, C.A., Dobbs, M., Morcuende, J.A., Szappanos, L., Herring, J.A., Bowcock, A.M. and Lovett, M. (2004) SNTG1, the Gene Encoding Gamma1-Syntrophin: A Candidate Gene for Idiopathic Scoliosis. Human Genetics, 115, 81-89. http://dx.doi.org/10.1007/s00439-004-1121-y
[33] Segel, L.D. and Ensunsa, J.L. (1988) Albumin Improves Stability and Longevity of Perfluorochemical-Perfused Hearts. The American Journal of Physiology, 254, 1105-1112.
[34] Gabant, P., Forrester, L., Nichols, J., Van Reeth, T., De Mees, C., Pajack, B., Watt, A., Smitz, J., Alexandre, H., Szpirer, C. and Szpirer, J. (2002) Alpha-Fetoprotein, the Major Fetal Serum Protein, Is Not Essential for Embryonic Development but Is Required for Female Fertility. Proceedings of the National Academy of Sciences of the United States of America, 99, 12865-12870.
[35] Le Goff, C. and Cormier-Daire, V. (2011) The ADAMTS(L) Family and Human Genetic Disorders. Human Molecular Genetics, 20, R163-R167. http://dx.doi.org/10.1093/hmg/ddr361
[36] Lee, C.W., Hwang, I., Park, C.S., Lee, H., Park, D.W., Kang, S.J., Lee, S.W., Kim, Y.H., Park, S.W. and Park, S.J. (2012) Expression of ADAMTS-2, -3, -13, and -14 in Culprit Coronary Lesions in Patients with Acute Myocardial Infarction or Stable Angina. Journal of Thrombosis and Thrombolysis, 33, 362-370.
[37] Chen, H.C., Kraus, V.B., Li, Y.J., Nelson, S., Haynes, C., Johnson, J., Stabler, T., Hauser, E.R., Gregory, S.G., Kraus, W.E. and Shah, S.H. (2010) Genome-Wide Linkage Analysis of Quantitative Biomarker Traits of Osteoarthritis in a Large, Multigenerational Extended Family. Arthritis and Rheumatism, 62, 781-790.
[38] Kishore, R., Luedemann, C., Bord, E., Goukassian, D. and Losordo, D.W. (2003) Tumor Necrosis Factor-Mediated E2F1 Suppression in Endothelial Cells: Differential Requirement of c-Jun N-Terminal Kinase and p38 Mitogen-Activated Protein Kinase Signal Transduction Pathways. Circulation Research, 93, 932-940.
[39] Cui, Z.W., Xia, Y., Ye, Y.W., Jiang, Z.M., Wang, Y.D., Wu, J.T., Sun, L., Zhao, J., Fa, P.P., Sun, X.J., Gui, Y.T. and Cai, Z.M. (2012) RALY RNA Binding Protein-Like Reduced Expression Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma. Asian Pacific Journal of Cancer Prevention, 13, 3403-3408.
[40] Heaney, J.D., Michelson, M.V., Youngren, K.K., Lam, M.Y. and Nadeau, J.H. (2009) Deletion of eIF2beta Suppresses Testicular Cancer Incidence and Causes Recessive Lethality in Agouti-Yellow Mice. Human Molecular Genetics, 18, 1395-1404. http://dx.doi.org/10.1093/hmg/ddp045
[41] Deak, F. and Sonntag, W.E. (2012) Aging, Synaptic Dysfunction, and Insulin-Like Growth Factor (IGF)-1. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 67A, 611-625.
[42] Ron-Harel, N., Segev, Y., Lewitus, G.M., Cardon, M., Ziv, Y., Netanely, D., Jacob-Hirsch, J., Amariglio, N., Rechavi, G., Domany, E. and Schwartz, M. (2008) Age-Dependent Spatial Memory Loss Can Be Partially Restored by Immune Activation. Rejuvenation Research, 11, 903-913. http://dx.doi.org/10.1089/rej.2008.0755
[43] Gupta, V.K., You, Y., Gupta, V.B., Klistorner, A. and Graham, S.L. (2013) TrkB Receptor Signalling: Implications in Neurodegenerative, Psychiatric and Proliferative Disorders. International Journal of Molecular Sciences, 14, 10122-10142. http://dx.doi.org/10.3390/ijms140510122
[44] Dissen, G.A., Hirshfield, A.N., Malamed, S. and Ojeda, S.R. (1995) Expression of Neurotrophins and Their Recaptors in the Mammalian Ovary Is Developmentally Regulated: Changes at the Time of Folliculogenesis. Endocrinology, 136, 4681-4692. http://dx.doi.org/10.1210/en.136.10.4681
[45] Li, C., Li, C., Zhu, X., Wang, C., Liu, Z., Li, W., Lu, C. and Zhou, X. (2012) The Expression and Putative Role of Brain-Derived Neurotrophic Factor and Its Receptor in Bovine Sperm. Theriogenology, 77, 636-643.
[46] Willcox, B.J., Donlon, T.A., He, Q., Chen, R., Grove, J.S., Yano, K., Masaki, K.H., Willcox, D.C., Rodriguez, B. and Curb, J.D. (2008) FOXO3A Genotype Is Strongly Associated with Human Longevity. Proceedings of the National Academy of Sciences of the United States of America, 105, 13987-13992.
[47] Flachsbart, F., Caliebe, A., Kleindorp, R., Blanché, H., von Eller-Eberstein, H., Nikolaus, S., Schreiber, S. and Nebel, A. (2009) Association of FOXO3A Variation with Human Longevity Confirmed in German Centenarians. Proceedings of the National Academy of Sciences, 106, 2700-2705. http://dx.doi.org/10.1073/pnas.0809594106
[48] Donlon, T.A., Curb, J.D., He, Q., Grove, J.S., Masaki, K.H., Rodriguez, B., Elliott, A., Willcox, D.C. and Willcox, B.J. (2012) FOXO3 Gene Variants and Human Aging: Coding Variants May Not Be Key Players. Journal of Gerontology: Biological Sciences, 67, 1132-1139.
[49] Schächter, F., Faure-Delanef, L., Guénot, F., Rouger, H., Froguel, P., Lesueur-Ginot, L. and Cohen, D. (1994) Genetic Associations with Human Longevity at the APOE and ACE Loci. Nature Genetics, 6, 29-32.
[50] Takahashi, Y., Sato, K., Itoh, F., Miyamoto, T., Oohashi, T. and Katoh, N. (2003) Bovine Apolipoprotein E in Plasma: Increase of ApoE Concentration Induced by Fasting and Distribution in Lipoprotein Fractions. The Journal of Veterinary Medical Science, 65, 199-205. http://dx.doi.org/10.1292/jvms.65.199
[51] Takahashi, Y., Itoh, F., Oohashi, T. and Miyamoto, T. (2003) Distribution of Apolipoprotein E among Lipoprotein Fractions in the Lactating Cow. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 136, 905-912. http://dx.doi.org/10.1016/j.cbpc.2003.09.004
[52] Kremmidiotis, G., Baker, E., Crawford, J., Eyre, H.J., Nahmias, J. and Callen, D.F. (1998) Localization of Human Cadherin Genes to Chromosome Regions Exhibiting Cancer-Related Loss of Heterozygosity. Genomics, 49, 467-471.
[53] Wang, J.F., She, L., Su, B.H., Ding, L.C., Zheng, F.F., Zheng, D.L. and Lu, Y.G. (2011) CDH12 Promotes the Invasion of Salivary Adenoid Cystic Carcinoma. Oncology Reports, 26, 101-108.
[54] Johansson, A., Curran, J.E., Johnson, M.P., Freed, K.A., Fenstad, M.H., Bjørge, L., Eide, I.P., Carless, M.A., Rainwater, D.L., Goring, H.H., Austgulen, R., Moses, E.K. and Blangero, J. (2011) Identification of ACOX2 as a Shared Genetic Risk Factor for Preeclampsia and Cardiovascular Disease. European Journal of Human Genetics, 19, 796-800.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.