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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Age of Onset

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Disease relevance of Age of Onset


Psychiatry related information on Age of Onset


High impact information on Age of Onset

  • A related challenge is to determine the degree to which each pathogenic variant impairs ABCR function, as genotype-phenotype analyses indicate that age of onset and disease severity correlate with different ABCA4 alleles [11].
  • Unlike MODY3 families, the Finnish families with low insulin have an age-of-onset typical for NIDDM (mean = 58 years) [12].
  • The steep inverse correlation between age of onset and CAG number suggests a higher sensitivity to polyglutamine length than in the other polyglutamine expansion diseases [13].
  • Maturity-onset diabetes of the young, a form of NIDDM with an early age of onset and autosomal dominant inheritance, can result from mutations in glucokinase, a key enzyme of glucose metabolism in beta cells and the liver [14].
  • We have assessed 360 HD individuals from 259 unrelated families and found a highly significant correlation (r = 0.70, p = 10(-7)) between the age of onset and the repeat length, which accounts for approximately 50% of the variation in the age of onset [15].

Chemical compound and disease context of Age of Onset

  • Retrospective study of 129 patients treated with dopamine substitution showed that the occurrence of response variations is related to the duration of therapy and not to the nature of the predominant symptom (tremor or hypokinesia and rigidity) or the age of onset of the disease [16].
  • Further heterogeneity is being demonstrated within each of these broad groups of disorders--within insulin-dependent diabetes using the HLA antigens and immunologic studies, and within noninsulin-dependent diabetes using such criteria as obesity, insulin response, age of onset and chlorpropamide-primed alcohol-induced flushing [17].
  • Results: No significant evidence of association between alleles of the serotonin transporter gene and pulmonary hypertension was detected, nor did we observe a relationship with age of onset in familial and idiopathic disease [18].
  • Although we confirm the previously reported correlation between the CAG repeat length and the early onset of the neurological disease, we describe a significant correlation between repeat length and the age of onset of gynecomastia as well as biological indexes of androgen insensitivity [19].
  • In the present studies, we have extended previous work by determining maturational patterns of the deiodinating pathways in several thyroid hormone-responsive rat tissues, possible modulation of those patterns by glucocorticoids, and the age of onset of responsivity of the deiodinases to hypothyroidism [20].

Biological context of Age of Onset


Anatomical context of Age of Onset


Associations of Age of Onset with chemical compounds

  • The age of onset of mammary tumors was also earlier after neonatal steroid treatment [31].
  • The male MZ/DZ concordance difference for composite diagnosis but not for Alcohol Dependence could be accounted for statistically by differences in age of onset between MZ and DZ probands [32].
  • Interestingly, we detected in the same region overlapping linkages with three QTLs: age of onset of CHD (LOD = 2.03), HDL cholesterol (LOD = 1.48) and LDL/HDL ratio (LOD = 1.34) [33].
  • The low doses of 17beta-estradiol and progesterone each resulted in an earlier age of onset and a higher incidence of mammary tumors; this also occurred after both combined estrogen-progesterone treatments [34].
  • Otherwise, clinical characteristics of PD in the kindred, including variance in onset age and incidence of tremor and levodopa responsiveness, are similar to those of PD in the community [35].

Gene context of Age of Onset

  • While the biological basis for the association of APOE epsilon4 with AD is not known, age of onset and A beta deposition are positively correlated with epsilon4 allele dosage in some cases, suggesting that this risk may also be mediated directly or indirectly through A beta [36].
  • The wide variability in the age of onset of ILD in patients with SFTPC mutations may be related to environmental insults that ultimately overwhelm the homeostatic cytoprotective response [37].
  • Inheritance of specific apolipoprotein E (apoE) alleles determines, in large part, the risk and mean age of onset of late-onset familial and sporadic Alzheimer disease [38].
  • In contrast, Tg(Dpl)ZrchI mice showed cerebellar granule and Purkinje cell loss; the age of onset of ataxia was inversely proportional to the levels of Dpl protein [39].
  • Analysis of additional members of a pedigree known to segregate a Met239Val mutation in PS-2 revealed that the age of onset of symptoms is highly variable (range 45-88 years) [40].

Analytical, diagnostic and therapeutic context of Age of Onset


  1. Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis. Sohocki, M.M., Bowne, S.J., Sullivan, L.S., Blackshaw, S., Cepko, C.L., Payne, A.M., Bhattacharya, S.S., Khaliq, S., Qasim Mehdi, S., Birch, D.G., Harrison, W.R., Elder, F.F., Heckenlively, J.R., Daiger, S.P. Nat. Genet. (2000) [Pubmed]
  2. Deletion of the donor splice site of intron 4 in the glucokinase gene causes maturity-onset diabetes of the young. Sun, F., Knebelmann, B., Pueyo, M.E., Zouali, H., Lesage, S., Vaxillaire, M., Passa, P., Cohen, D., Velho, G., Antignac, C. J. Clin. Invest. (1993) [Pubmed]
  3. Liver biopsy discloses a new apolipoprotein A-I hereditary amyloidosis in several unrelated Italian families. Obici, L., Palladini, G., Giorgetti, S., Bellotti, V., Gregorini, G., Arbustini, E., Verga, L., Marciano, S., Donadei, S., Perfetti, V., Calabresi, L., Bergonzi, C., Scolari, F., Merlini, G. Gastroenterology (2004) [Pubmed]
  4. Genetic flanking markers refine diagnostic criteria and provide insights into the genetics of Von Hippel Lindau disease. Seizinger, B.R., Smith, D.I., Filling-Katz, M.R., Neumann, H., Green, J.S., Choyke, P.L., Anderson, K.M., Freiman, R.N., Klauck, S.M., Whaley, J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  5. Analysis of the dynamic mutation in the SCA7 gene shows marked parental effects on CAG repeat transmission. Gouw, L.G., Castañeda, M.A., McKenna, C.K., Digre, K.B., Pulst, S.M., Perlman, S., Lee, M.S., Gomez, C., Fischbeck, K., Gagnon, D., Storey, E., Bird, T., Jeri, F.R., Ptácek, L.J. Hum. Mol. Genet. (1998) [Pubmed]
  6. Huntington's disease age-of-onset linked to polyglutamine aggregation nucleation. Chen, S., Ferrone, F.A., Wetzel, R. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  7. Apolipoprotein E genotypes in Parkinson's disease with and without dementia. Koller, W.C., Glatt, S.L., Hubble, J.P., Paolo, A., Tröster, A.I., Handler, M.S., Horvat, R.T., Martin, C., Schmidt, K., Karst, A. Ann. Neurol. (1995) [Pubmed]
  8. Developmental expression of mucin genes in the human gastrointestinal system. Reid, C.J., Harris, A. Gut (1998) [Pubmed]
  9. Factors predicting the onset of adolescent drinking in families at high risk for developing alcoholism. Hill, S.Y., Shen, S., Lowers, L., Locke, J. Biol. Psychiatry (2000) [Pubmed]
  10. Apolipoprotein E epsilon 4 allele and Japanese late-onset depressive disorders. Ohara, K., Nagai, M., Suzuki, Y., Yoshida, K., Tsukamoto, T., Ohara, K. Biol. Psychiatry (1999) [Pubmed]
  11. Biochemical defects in ABCR protein variants associated with human retinopathies. Sun, H., Smallwood, P.M., Nathans, J. Nat. Genet. (2000) [Pubmed]
  12. Mapping of a gene for type 2 diabetes associated with an insulin secretion defect by a genome scan in Finnish families. Mahtani, M.M., Widén, E., Lehto, M., Thomas, J., McCarthy, M., Brayer, J., Bryant, B., Chan, G., Daly, M., Forsblom, C., Kanninen, T., Kirby, A., Kruglyak, L., Munnelly, K., Parkkonen, M., Reeve-Daly, M.P., Weaver, A., Brettin, T., Duyk, G., Lander, E.S., Groop, L.C. Nat. Genet. (1996) [Pubmed]
  13. Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Imbert, G., Saudou, F., Yvert, G., Devys, D., Trottier, Y., Garnier, J.M., Weber, C., Mandel, J.L., Cancel, G., Abbas, N., Dürr, A., Didierjean, O., Stevanin, G., Agid, Y., Brice, A. Nat. Genet. (1996) [Pubmed]
  14. Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus. Froguel, P., Zouali, H., Vionnet, N., Velho, G., Vaxillaire, M., Sun, F., Lesage, S., Stoffel, M., Takeda, J., Passa, P. N. Engl. J. Med. (1993) [Pubmed]
  15. The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Andrew, S.E., Goldberg, Y.P., Kremer, B., Telenius, H., Theilmann, J., Adam, S., Starr, E., Squitieri, F., Lin, B., Kalchman, M.A. Nat. Genet. (1993) [Pubmed]
  16. Factors that influence the occurrence of response variations in Parkinson's disease. de Jong, G.J., Meerwaldt, J.D., Schmitz, P.I. Ann. Neurol. (1987) [Pubmed]
  17. The genetics of the glucose intolerance disorders. Rotter, J.I., Rimoin, D.L. Am. J. Med. (1981) [Pubmed]
  18. Genetic association of the serotonin transporter in pulmonary arterial hypertension. Machado, R.D., Koehler, R., Glissmeyer, E., Veal, C., Suntharalingam, J., Kim, M., Carlquist, J., Town, M., Elliott, C.G., Hoeper, M., Fijalkowska, A., Kurzyna, M., Thomson, J.R., Gibbs, S.R., Wilkins, M.R., Seeger, W., Morrell, N.W., Gruenig, E., Trembath, R.C., Janssen, B. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
  19. A comprehensive endocrine description of Kennedy's disease revealing androgen insensitivity linked to CAG repeat length. Dejager, S., Bry-Gauillard, H., Bruckert, E., Eymard, B., Salachas, F., LeGuern, E., Tardieu, S., Chadarevian, R., Giral, P., Turpin, G. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  20. Iodothyronine deiodination reaction types in several rat tissues: effects of age, thyroid status, and glucocorticoid treatment. McCann, U.D., Shaw, E.A., Kaplan, M.M. Endocrinology (1984) [Pubmed]
  21. Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus. Froguel, P., Vaxillaire, M., Sun, F., Velho, G., Zouali, H., Butel, M.O., Lesage, S., Vionnet, N., Clément, K., Fougerousse, F. Nature (1992) [Pubmed]
  22. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Rogaev, E.I., Sherrington, R., Rogaeva, E.A., Levesque, G., Ikeda, M., Liang, Y., Chi, H., Lin, C., Holman, K., Tsuda, T. Nature (1995) [Pubmed]
  23. Primary familial bilateral carpal tunnel syndrome. Gray, R.G., Poppo, M.J., Gottlieb, N.L. Ann. Intern. Med. (1979) [Pubmed]
  24. Genotypes at the GluR6 kainate receptor locus are associated with variation in the age of onset of Huntington disease. Rubinsztein, D.C., Leggo, J., Chiano, M., Dodge, A., Norbury, G., Rosser, E., Craufurd, D. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  25. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Wexler, N.S., Lorimer, J., Porter, J., Gomez, F., Moskowitz, C., Shackell, E., Marder, K., Penchaszadeh, G., Roberts, S.A., Gayán, J., Brocklebank, D., Cherny, S.S., Cardon, L.R., Gray, J., Dlouhy, S.R., Wiktorski, S., Hodes, M.E., Conneally, P.M., Penney, J.B., Gusella, J., Cha, J.H., Irizarry, M., Rosas, D., Hersch, S., Hollingsworth, Z., MacDonald, M., Young, A.B., Andresen, J.M., Housman, D.E., De Young, M.M., Bonilla, E., Stillings, T., Negrette, A., Snodgrass, S.R., Martinez-Jaurrieta, M.D., Ramos-Arroyo, M.A., Bickham, J., Ramos, J.S., Marshall, F., Shoulson, I., Rey, G.J., Feigin, A., Arnheim, N., Acevedo-Cruz, A., Acosta, L., Alvir, J., Fischbeck, K., Thompson, L.M., Young, A., Dure, L., O'Brien, C.J., Paulsen, J., Brickman, A., Krch, D., Peery, S., Hogarth, P., Higgins, D.S., Landwehrmeyer, B. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  26. Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease. Poirier, J., Delisle, M.C., Quirion, R., Aubert, I., Farlow, M., Lahiri, D., Hui, S., Bertrand, P., Nalbantoglu, J., Gilfix, B.M., Gauthier, S. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  27. Familial diabetes mellitus with variable B cell reserve; analysis of a pedigree. Bodansky, H.J., Kelly, W.F. Diabetologia (1987) [Pubmed]
  28. Role of gender and hormone-related events on IgE, atopy, and eosinophils in the Epidemiological Study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy. Siroux, V., Curt, F., Oryszczyn, M.P., Maccario, J., Kauffmann, F. J. Allergy Clin. Immunol. (2004) [Pubmed]
  29. Hprt(CAG)146 mice: age of onset of behavioral abnormalities, time course of neuronal intranuclear inclusion accumulation, neurotransmitter marker alterations, mitochondrial function markers, and susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Tallaksen-Greene, S.J., Ordway, J.M., Crouse, A.B., Jackson, W.S., Detloff, P.J., Albin, R.L. J. Comp. Neurol. (2003) [Pubmed]
  30. The neurodevelopmental impact of childhood-onset temporal lobe epilepsy on brain structure and function. Hermann, B., Seidenberg, M., Bell, B., Rutecki, P., Sheth, R., Ruggles, K., Wendt, G., O'Leary, D., Magnotta, V. Epilepsia (2002) [Pubmed]
  31. Long-term effects of neonatal steroid exposure on mammary gland development and tumorigenesis in mice. Mori, T., Bern, H.A., Mills, K.T., Young, P.N. J. Natl. Cancer Inst. (1976) [Pubmed]
  32. Heterogeneity in the inheritance of alcoholism. A study of male and female twins. Pickens, R.W., Svikis, D.S., McGue, M., Lykken, D.T., Heston, L.L., Clayton, P.J. Arch. Gen. Psychiatry (1991) [Pubmed]
  33. A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q27. Francke, S., Manraj, M., Lacquemant, C., Lecoeur, C., Leprêtre, F., Passa, P., Hebe, A., Corset, L., Yan, S.L., Lahmidi, S., Jankee, S., Gunness, T.K., Ramjuttun, U.S., Balgobin, V., Dina, C., Froguel, P. Hum. Mol. Genet. (2001) [Pubmed]
  34. Long-term effects of neonatal treatment with progesterone, alone and in combination with estrogen, on the mammary gland and reproductive tract of female BALB/cfC3H mice. Jones, L.A., Bern, H.A. Cancer Res. (1977) [Pubmed]
  35. Clinical genetic analysis of Parkinson's disease in the Contursi kindred. Golbe, L.I., Di Iorio, G., Sanges, G., Lazzarini, A.M., La Sala, S., Bonavita, V., Duvoisin, R.C. Ann. Neurol. (1996) [Pubmed]
  36. Exploring the etiology of Alzheimer disease using molecular genetics. Lendon, C.L., Ashall, F., Goate, A.M. JAMA (1997) [Pubmed]
  37. Adaptation and increased susceptibility to infection associated with constitutive expression of misfolded SP-C. Bridges, J.P., Xu, Y., Na, C.L., Wong, H.R., Weaver, T.E. J. Cell Biol. (2006) [Pubmed]
  38. Apolipoprotein E and Alzheimer disease. Strittmatter, W.J., Roses, A.D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  39. Doppel-induced cerebellar degeneration in transgenic mice. Moore, R.C., Mastrangelo, P., Bouzamondo, E., Heinrich, C., Legname, G., Prusiner, S.B., Hood, L., Westaway, D., DeArmond, S.J., Tremblay, P. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  40. Alzheimer's disease associated with mutations in presenilin 2 is rare and variably penetrant. Sherrington, R., Froelich, S., Sorbi, S., Campion, D., Chi, H., Rogaeva, E.A., Levesque, G., Rogaev, E.I., Lin, C., Liang, Y., Ikeda, M., Mar, L., Brice, A., Agid, Y., Percy, M.E., Clerget-Darpoux, F., Piacentini, S., Marcon, G., Nacmias, B., Amaducci, L., Frebourg, T., Lannfelt, L., Rommens, J.M., St George-Hyslop, P.H. Hum. Mol. Genet. (1996) [Pubmed]
  41. Apparent different thrombotic tendency in patients with factor V Leiden and protein C deficiency due to selection of patients. Lensen, R.P., Rosendaal, F.R., Koster, T., Allaart, C.F., de Ronde, H., Vandenbroucke, J.P., Reitsma, P.H., Bertina, R.M. Blood (1996) [Pubmed]
  42. Tuberous sclerosis with striking renal involvement in a family. O'Callaghan, T.J., Edwards, J.A., Tobin, M., Mookerjee, B.K. Arch. Intern. Med. (1975) [Pubmed]
  43. Age of onset and type of diabetes. Laakso, M., Pyörälä, K. Diabetes Care (1985) [Pubmed]
  44. Evidence for the role of gonadotropin hormones in the development of Alzheimer disease. Casadesus, G., Atwood, C.S., Zhu, X., Hartzler, A.W., Webber, K.M., Perry, G., Bowen, R.L., Smith, M.A. Cell. Mol. Life Sci. (2005) [Pubmed]
  45. Alpha 1-antitrypsin deficiency alleles in cystic fibrosis lung disease. Frangolias, D.D., Ruan, J., Wilcox, P.J., Davidson, A.G., Wong, L.T., Berthiaume, Y., Hennessey, R., Freitag, A., Pedder, L., Corey, M., Sweezey, N., Zielenski, J., Tullis, E., Sandford, A.J. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
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