Genetics of tinnitus: An emerging area for molecular diagnosis and drug development

Frontiers in Neuroscience

Volumn 10, Issue AUG, 2016, Pages

  Lopez Escamez, Jose A ^a,b   Bibas, Thanos ^c,d   Cima, Rilana F F ^e   Van de Heyning, Paul ^f   Knipper, Marlies ^g   Mazurek, Birgit ^h   Szczepek, Agnieszka J ^h   Cederroth, Christopher R ⁱ  

^a PTS Granada   (Spain)

^b UNIVERSITY OF GRANADA   (Spain)

^c UNIVERSITY OF ATHENS   (Greece)

^d UNIVERSITY COLLEGE LONDON   (United Kingdom)

^e MAASTRICHT UNIVERSITY   (Netherlands)

^f ANTWERP UNIVERSITY HOSPITAL   (Belgium)

^g UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^h CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

ⁱ KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Epidemiology; Genetic; Hearing loss; Meniere's disease; Phenotyping; Subtype; Tinnitus

Indexed keywords

DRUG RESEARCH; EPIGENETICS; EXOME; GENE SEQUENCE; GENETIC ANALYSIS; GENETIC ASSOCIATION; HEARING IMPAIRMENT; HERITABILITY; HUMAN; MENIERE DISEASE; MOLECULAR DIAGNOSIS; NONHUMAN; PATHOPHYSIOLOGY; PHENOTYPE; REVIEW; SEQUENCE ANALYSIS; TINNITUS;

EID: 84988354524     PISSN: 16624548     EISSN: 1662453X     Source Type: Journal    
DOI: 10.3389/fnins.2016.00377     Document Type: Review

References (121)

1. Andersson, G. (2003). Tinnitus loudness matchings in relation to annoyance and grading of severity. Auris Nasus Larynx 30, 129-133. doi: 10.1016/S0385-8146(03)00008-7.
2. Anway, M. D., Cupp, A. S., Uzumcu, M., and Skinner, M. K. (2005). Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308, 1466-1469. doi: 10.1126/science.1108190.
3. Ayache, D., Earally, F., and Elbaz, P. (2003). Characteristics and postoperative course of tinnitus in otosclerosis. Otol. Neurotol. 24, 48-51. doi: 10.1097/00129492-200301000-00011.
4. Bagot, R. C., Labonté, B., Peña, C. J., and Nestler, E. J. (2014). Epigenetic signaling in psychiatric disorders: stress and depression. Dialogues Clin. Neurosci. 16, 281-295.
5. Baguley, D. M. (2003). Hyperacusis. J. R. Soc. Med. 96, 582-585. doi: 10.1258/jrsm.96.12.582.
6. Baguley, D., McFerran, D., and Hall, D. (2013). Tinnitus. Lancet 382, 1600-1607. doi: 10.1016/S0140-6736(13)60142-7.
7. Biesecker, L. G., and Green, R. C. (2014). Diagnostic clinical genome and exome sequencing. N. Engl. J. Med. 371, 1170. doi: 10.1056/NEJMra1312543.
8. Bigal, M. E., Kolodner, K. B., Lafata, J. E., Leotta, C., and Lipton, R. B. (2006). Patterns of medical diagnosis and treatment of migraine and probable migraine in a health plan. Cephalalgia 26, 43-49. doi: 10.1111/j.1468-2982.2005.00988.x.
9. Bitsch, A., and Brück, W. (2002). Differentiation of multiple sclerosis subtypes: implications for treatment. CNS Drugs 16, 405-418. doi: 10.2165/00023210-200216060-00004.
10. Bohacek, J., and Mansuy, I. M. (2015). Molecular insights into transgenerational non-genetic inheritance of acquired behaviours. Nat. Rev. Genet. 16, 641-652. doi: 10.1038/nrg3964.
11. Bozdagi, O., Tavassoli, T., and Buxbaum, J. D. (2013). Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay. Mol. Autism 4:9. doi: 10.1186/2040-2392-4-9.
12. Bredesen, D. E. (2015). Metabolic profiling distinguishes three subtypes of Alzheimers disease. Aging 7, 595-600. doi: 10.18632/aging.100801.
13. Cederroth, C. R., Canlon, B., and Langguth, B. (2013). Hearing loss and tinnitus-are funders and industry listening? Nat. Biotechnol. 31, 972-974. doi: 10.1038/nbt.2736.
14. Cederroth, C. R., Vassalli, J. D., and Nef, S. (2007). [Of epigenetics and development]. Rev. Med. Suisse 3, 528, 530-522.
15. Cheung, S. W., and Larson, P. S. (2010). Tinnitus modulation by deep brain stimulation in locus of caudate neurons (area LC). Neuroscience 169, 1768-1778. doi: 10.1016/j.neuroscience.2010.06.007.
16. Cianfrone, G., Mazzei, F., Salviati, M., Turchetta, R., Orlando, M. P., Testugini, V., et al. (2015). Tinnitus Holistic Simplified Classification (THoSC): a new assessment for subjective tinnitus, with diagnostic and therapeutic implications. Ann. Otol. Rhinol. Laryngol. 124, 550-560. doi: 10.1177/0003489415570931.
17. Cima, R. F., Maes, I. H., Joore, M. A., Scheyen, D. J., El Refaie, A., Baguley, D. M., et al. (2012). Specialised treatment based on cognitive behaviour therapy versus usual care for tinnitus: a randomised controlled trial. Lancet 379, 1951-1959. doi: 10.1016/S0140-6736(12)60469-3.
18. CONVERGE, C. (2015). Sparse whole-genome sequencing identifies two loci for major depressive disorder. Nature 523, 588-591. doi: 10.1038/nature14659.
19. Cooper, G. M., and Shendure, J. (2011). Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data. Nat. Rev. Genet. 12, 628-640. doi: 10.1038/nrg3046.
20. Cooper, J. C. Jr. (1994). Health and nutrition examination survey of 1971-1975: part II. tinnitus, subjective hearing loss, and well-being. J. Am. Acad. Audiol. 5, 37-43.
21. Davis, A., and Refaie, A. E. (2000). "Epidemiology of tinnitus," in The Handbook of Tinnitus, ed R. S. Tyler (San Diego, CA: Singular Thompson Learning), 1-23.
22. Deniz, M., Bayazit, Y. A., Celenk, F., Karabulut, H., Yilmaz, A., Gunduz, B., et al. (2010). Significance of serotonin transporter gene polymorphism in tinnitus. Otol. Neurotol. 31, 19-24. doi: 10.1097/MAO.0b013e3181c2dcbc.
23. Don, M., and Eggermont, J. J. (1978). Analysis of the click-evoked brainstem potentials in man unsing high-pass noise masking. J. Acoust. Soc. Am. 63, 1084-1092. doi: 10.1121/1.381816.
24. Drevets, W. C., Price, J. L., and Furey, M. L. (2008). Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Struct. Funct. 213, 93-118. doi: 10.1007/s00429-008-0189-x.
25. Eggermont, J. J., and Don, M. (1980). Analysis of the click-evoked brainstem potentials in humans using high-pass noise masking. II. Effect of click intensity. J. Acoust. Soc. Am. 68, 1671-1675. doi: 10.1121/1.385199.
26. Elgoyhen, A. B., Langguth, B., De Ridder, D., and Vanneste, S. (2015). Tinnitus: perspectives from human neuroimaging. Nat. Rev. Neurosci. 16, 632-642. doi: 10.1038/nrn4003.
27. Engdahl, B., Krog, N. H., Kvestad, E., Hoffman, H. J., and Tambs, K. (2012). Occupation and the risk of bothersome tinnitus: results from a prospective cohort study (HUNT). BMJ Open 2:e000512. doi: 10.1136/bmjopen-2011-000512.
28. Erlandsson, S. I., and Hallberg, L. R. (2000). Prediction of quality of life in patients with tinnitus. Br. J. Audiol. 34, 11-20. doi: 10.3109/03005364000000114.
29. Franklin, T. B., Russig, H., Weiss, I. C., Gräff, J., Linder, N., Michalon, A., et al. (2010). Epigenetic transmission of the impact of early stress across generations. Biol. Psychiatry 68, 408-415. doi: 10.1016/j.biopsych.2010.05.036.
30. Franklin, T. B., Saab, B. J., and Mansuy, I. M. (2012). Neural mechanisms of stress resilience and vulnerability. Neuron 75, 747-761. doi: 10.1016/j.neuron.2012.08.016.
31. Fransen, E., Bonneux, S., Corneveaux, J. J., Schrauwen, I., Di Berardino, F., White, C. H., et al. (2015). Genome-wide association analysis demonstrates the highly polygenic character of age-related hearing impairment. Eur. J. Hum. Genet. 23, 110-115. doi: 10.1038/ejhg.2014.56.
32. Friberg, E., Jansson, C., Mittendorfer-Rutz, E., Rosenhall, U., and Alexanderson, K. (2012). Sickness absence due to otoaudiological diagnoses and risk of disability pension: a nationwide Swedish prospective cohort study. PLoS ONE 7:e29966. doi: 10.1371/journal.pone.0029966.
33. Fuchikami, M., Yamamoto, S., Morinobu, S., Takei, S., and Yamawaki, S. (2010). Epigenetic regulation of BDNF gene in response to stress. Psychiatry Investig. 7, 251-256. doi: 10.4306/pi.2010.7.4.251.
34. Gallant, E., Francey, L., Fetting, H., Kaur, M., Hakonarson, H., Clark, D., et al. (2013). Novel COCH mutation in a family with autosomal dominant late onset sensorineural hearing impairment and tinnitus. Am. J. Otolaryngol. 34, 230-235. doi: 10.1016/j.amjoto.2012.11.002.
35. Gallus, S., Lugo, A., Garavello, W., Bosetti, C., Santoro, E., Colombo, P., et al. (2015). Prevalence and determinants of tinnitus in the italian adult population. Neuroepidemiology 45, 12-19. doi: 10.1159/000431376.
36. Gelernter, J., Panhuysen, C., Wilcox, M., Hesselbrock, V., Rounsaville, B., Poling, J., et al. (2006). Genomewide linkage scan for opioid dependence and related traits. Am. J. Hum. Genet. 78, 759-769. doi: 10.1086/503631.
37. Gersdorff, M., Nouwen, J., Gilain, C., Decat, M., and Betsch, C. (2000). Tinnitus and otosclerosis. Eur. Arch. Otorhinolaryngol. 257, 314-316. doi: 10.1007/s004059900138.
38. Goldman, D. R., and Holme, R. (2010). Hearing loss and tinnitus-the hidden healthcare time bomb. Drug Discov. Today 15, 253-255. doi: 10.1016/j.drudis.2010.01.010.
39. Gopinath, B., McMahon, C. M., Rochtchina, E., Karpa, M. J., and Mitchell, P. (2010). Incidence, persistence, and progression of tinnitus symptoms in older adults: the Blue Mountains Hearing Study. Ear Hear. 31, 407-412. doi: 10.1097/AUD.0b013e3181cdb2a2.
40. Hall, D. A., Haider, H., Kikidis, D., Mielczarek, M., Mazurek, B., Szczepek, A. J., et al. (2015). Toward a global consensus on outcome measures for clinical trials in tinnitus: report from the first international meeting of the COMiT Initiative, November 14, 2014, Amsterdam, The Netherlands. Trends Hear 19:2331216515580272. doi: 10.1177/2331216515580272.
41. Hasson, D., Theorell, T., Westerlund, H., and Canlon, B. (2010). Prevalence and characteristics of hearing problems in a working and non-working Swedish population. J. Epidemiol. Community Health 64, 453-460. doi: 10.1136/jech.2009.095430.
42. Hébert, S., Canlon, B., Hasson, D., Magnusson Hanson, L. L., Westerlund, H., and Theorell, T. (2012). Tinnitus severity is reduced with reduction of depressive mood-a prospective population study in Sweden. PLoS ONE 7:e37733. doi: 10.1371/journal.pone.0037733.
43. Hébert, S., and Lupien, S. J. (2007). The sound of stress: blunted cortisol reactivity to psychosocial stress in tinnitus sufferers. Neurosci. Lett. 411, 138-142. doi: 10.1016/j.neulet.2006.10.028.
44. Heinonen-Guzejev, M., Vuorinen, H. S., Mussalo-Rauhamaa, H., Heikkilä, K., Koskenvuo, M., and Kaprio, J. (2005). Genetic component of noise sensitivity. Twin Res. Hum. Genet. 8, 245-249. doi: 10.1375/twin.8.3.245.
45. Hendrickx, J. J., Huyghe, J. R., Demeester, K., Topsakal, V., Van Eyken, E., Fransen, E., et al. (2007). Familial aggregation of tinnitus: a European multicentre study. B-ENT 3(Suppl. 7), 51-60.
46. Henry, J. A., and Meikle, M. B. (2000). Psychoacoustic measures of tinnitus. J. Am. Acad. Audiol. 11, 138-155.
47. Hiller, W., and Goebel, G. (2007). When tinnitus loudness and annoyance are discrepant: audiological characteristics and psychological profile. Audiol. Neurootol. 12, 391-400. doi: 10.1159/000106482.
48. International HapMap, C. (2003). The international hapmap project. Nature 426, 789-796. doi: 10.1038/nature02168.
49. Jaenisch, R. (1997). DNA methylation and imprinting: why bother? Trends Genet. 13, 323-329. doi: 10.1016/S0168-9525(97)01180-3.
50. Jastreboff, P. J. (1990). Phantom auditory perception (tinnitus): mechanisms of generation and perception. Neurosci. Res. 8, 221-254. doi: 10.1016/0168-0102(90)90031-9.
51. Jastreboff, P. J., and Hazell, J. W. (1993). A neurophysiological approach to tinnitus: clinical implications. Br. J. Audiol. 27, 7-17. doi: 10.3109/03005369309077884.
52. Khedr, E. M., Ahmed, M. A., Shawky, O. A., Mohamed, E. S., El Attar, G. S., and Mohammad, K. A. (2010). Epidemiological study of chronic tinnitus in Assiut, Egypt. Neuroepidemiology 35, 45-52. doi: 10.1159/000306630.
53. Knipper, M., Van Dijk, P., Nunes, I., Rüttiger, L., and Zimmermann, U. (2013). Advances in the neurobiology of hearing disorders: recent developments regarding the basis of tinnitus and hyperacusis. Prog. Neurobiol. 111, 17-33. doi: 10.1016/j.pneurobio.2013.08.002.
54. Kolevzon, A., Bush, L., Wang, A. T., Halpern, D., Frank, Y., Grodberg, D., et al. (2014). A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome. Mol. Autism 5:54. doi: 10.1186/2040-2392-5-54.
55. Kolodner, K., Lipton, R. B., Lafata, J. E., Leotta, C., Liberman, J. N., Chee, E., et al. (2004). Pharmacy and medical claims data identified migraine sufferers with high specificity but modest sensitivity. J. Clin. Epidemiol. 57, 962-972. doi: 10.1016/j.jclinepi.2004.01.014.
56. Krog, N. H., Engdahl, B., and Tambs, K. (2010). The association between tinnitus and mental health in a general population sample: results from the HUNT Study. J. Psychosom. Res. 69, 289-298. doi: 10.1016/j.jpsychores.2010.03.008.
57. Kröner-Herwig, B., Frenzel, A., Fritsche, G., Schilkowsky, G., and Esser, G. (2003). The management of chronic tinnitus: comparison of an outpatient cognitive-behavioral group training to minimal-contact interventions. J. Psychosom. Res. 54, 381-389. doi: 10.1016/S0022-3999(02)00400-2.
58. Kvestad, E., Czajkowski, N., Engdahl, B., Hoffman, H. J., and Tambs, K. (2010). Low heritability of tinnitus: results from the second Nord-Trondelag health study. Arch. Otolaryngol. Head Neck Surg. 136, 178-182. doi: 10.1001/archoto.2009.220.
59. Landgrebe, M., Langguth, B., Rosengarth, K., Braun, S., Koch, A., Kleinjung, T., et al. (2009). Structural brain changes in tinnitus: grey matter decrease in auditory and non-auditory brain areas. Neuroimage 46, 213-218. doi: 10.1016/j.neuroimage.2009.01.069.
60. Landgrebe, M., Zeman, F., Koller, M., Eberl, Y., Mohr, M., Reiter, J., et al. (2010). The Tinnitus Research Initiative (TRI) database: a new approach for delineation of tinnitus subtypes and generation of predictors for treatment outcome. BMC Med. Inform. Decis. Mak. 10:42. doi: 10.1186/1472-6947-10-42.
61. Langguth, B., Goodey, R., Azevedo, A., Bjorne, A., Cacace, A., Crocetti, A., et al. (2007). Consensus for tinnitus patient assessment and treatment outcome measurement: tinnitus research initiative meeting, Regensburg, July 2006. Prog. Brain Res. 166, 525-536. doi: 10.1016/S0079-6123(07)66050-6.
62. Langguth, B., Kreuzer, P. M., Kleinjung, T., and De Ridder, D. (2013). Tinnitus: causes and clinical management. Lancet Neurol. 12, 920-930. doi: 10.1016/S1474-4422(13)70160-1.
63. Lasisi, A. O., Abiona, T., and Gureje, O. (2010). Tinnitus in the elderly: profile, correlates, and impact in the Nigerian Study of Ageing. Otolaryngol. Head Neck Surg. 143, 510-515. doi: 10.1016/j.otohns.2010.06.817.
64. Leaver, A. M., Renier, L., Chevillet, M. A., Morgan, S., Kim, H. J., and Rauschecker, J. P. (2011). Dysregulation of limbic and auditory networks in tinnitus. Neuron 69, 33-43. doi: 10.1016/j.neuron.2010.12.002.
65. Lesch, K. P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., et al. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527-1531. doi: 10.1126/science.274.5292.1527.
66. Levine, R. A., and Oron, Y. (2015). Tinnitus. Handb. Clin. Neurol. 129, 409-431. doi: 10.1016/B978-0-444-62630-1.00023-8.
67. Lipton, R. B., Scher, A. I., Steiner, T. J., Bigal, M. E., Kolodner, K., Liberman, J. N., et al. (2003). Patterns of health care utilization for migraine in England and in the United States. Neurology 60, 441-448. doi: 10.1212/WNL.60.3.441.
68. Lockwood, A. H., Salvi, R. J., Coad, M. L., Towsley, M. L., Wack, D. S., and Murphy, B. W. (1998). The functional neuroanatomy of tinnitus: evidence for limbic system links and neural plasticity. Neurology 50, 114-120. doi: 10.1212/WNL.50.1.114.
69. Lowry, L. D., Eisenman, L. M., and Saunders, J. C. (2004). An absence of tinnitus. Otol. Neurotol. 25, 474-478. doi: 10.1097/00129492-200407000-00013.
70. Mardis, E. R. (2008). Next-generation DNA sequencing methods. Annu. Rev. Genomics Hum. Genet. 9, 387-402. doi: 10.1146/annurev.genom.9.081307.164359.
71. Martín-Sierra, C., Requena, T., Frejo, L., Price, S. D., Gallego-Martinez, A., Batuecas-Caletrio, A., et al. (2016). A novel missense variant in PRKCB segregates low-frequency hearing loss in an autosomal dominant family with Meniere's disease. Hum. Mol. Genet. doi: 10.1093/hmg/ddw183. [Epub ahead of print].
72. Mayer, W., Niveleau, A., Walter, J., Fundele, R., and Haaf, T. (2000). Demethylation of the zygotic paternal genome. Nature 403, 501-502. doi: 10.1038/35000656.
73. Mazurek, B., Olze, H., Haupt, H., and Szczepek, A. J. (2010). The more the worse: the grade of noise-induced hearing loss associates with the severity of tinnitus. Int. J. Environ. Res. Public Health 7, 3071-3079. doi: 10.3390/ijerph7083071.
74. McCormack, A., Edmondson-Jones, M., Fortnum, H., Dawes, P., Middleton, H., Munro, K. J., et al. (2014). The prevalence of tinnitus and the relationship with neuroticism in a middle-aged UK population. J. Psychosom. Res. 76, 56-60. doi: 10.1016/j.jpsychores.2013.08.018.
75. Mertens, G., De Bodt, M., and Van de Heyning, P. (2016). Cochlear implantation as a long-term treatment for ipsilateral incapacitating tinnitus in subjects with unilateral hearing loss up to 10 years. Hear. Res. 331, 1-6. doi: 10.1016/j.heares.2015.09.016.
76. Michikawa, T., Nishiwaki, Y., Kikuchi, Y., Saito, H., Mizutari, K., Okamoto, M., et al. (2010). Prevalence and factors associated with tinnitus: a community-based study of Japanese elders. J. Epidemiol. 20, 271-276. doi: 10.2188/jea. JE20090121.
77. Mirz, F., Gjedde, A., Sødkilde-Jrgensen, H., and Pedersen, C. B. (2000). Functional brain imaging of tinnitus-like perception induced by aversive auditory stimuli. Neuroreport 11, 633-637. doi: 10.1097/00001756-200002280-00039.
78. Moffat, G., Adjout, K., Gallego, S., Thai-Van, H., Collet, L., and Noreña, A. J. (2009). Effects of hearing aid fitting on the perceptual characteristics of tinnitus. Hear. Res. 254, 82-91. doi: 10.1016/j.heares.2009.04.016.
79. Moisiadis, V. G., and Matthews, S. G. (2014). Glucocorticoids and fetal programming part 2: mechanisms. Nat. Rev. Endocrinol. 10, 403-411. doi: 10.1038/nrendo.2014.74.
80. Mühlau, M., Rauschecker, J. P., Oestreicher, E., Gaser, C., Röttinger, M., Wohlschläger, A. M., et al. (2006). Structural brain changes in tinnitus. Cereb. Cortex 16, 1283-1288. doi: 10.1093/cercor/bhj070.
81. Nicolas-Puel, C., Akbaraly, T., Lloyd, R., Berr, C., Uziel, A., Rebillard, G., et al. (2006). Characteristics of tinnitus in a population of 555 patients: specificities of tinnitus induced by noise trauma. Int. Tinnitus J. 12, 64-70.
82. Nondahl, D. M., Cruickshanks, K. J., Wiley, T. L., Klein, B. E., Klein, R., Chappell, R., et al. (2010). The ten-year incidence of tinnitus among older adults. Int. J. Audiol. 49, 580-585. doi: 10.3109/14992021003753508.
83. Olze, H., Gräbel, S., Haupt, H., Forster, U., and Mazurek, B. (2012). Extra benefit of a second cochlear implant with respect to health-related quality of life and tinnitus. Otol. Neurotol. 33, 1169-1175. doi: 10.1097/MAO.0b013e31825e799f.
84. Park, B., Choi, H. G., Lee, H. J., An, S. Y., Kim, S. W., Lee, J. S., et al. (2014). Analysis of the prevalence of and risk factors for tinnitus in a young population. Otol. Neurotol. 35, 1218-1222. doi: 10.1097/mao.0000000000000472.
85. Pawelczyk, M., Rajkowska, E., Kotylo, P., Dudarewicz, A., Van Camp, G., and Sliwinska-Kowalska, M. (2012). Analysis of inner ear potassium recycling genes as potential factors associated with tinnitus. Int. J. Occup. Med. Environ. Health 25, 356-364. doi: 10.2478/s13382-012-0061-3.
86. Pierzycki, R. H., McNamara, A. J., Hoare, D. J., and Hall, D. A. (2016). Whole scalp resting state EEG of oscillatory brain activity shows no parametric relationship with psychoacoustic and psychosocial assessment of tinnitus: a repeated measures study. Hear. Res. 331, 101-108. doi: 10.1016/j.heares.2015.11.003.
87. Price, A. L., Zaitlen, N. A., Reich, D., and Patterson, N. (2010). New approaches to population stratification in genome-wide association studies. Nat. Rev. Genet. 11, 459-463. doi: 10.1038/nrg2813.
88. Provenzano, M. J., and Domann, F. E. (2007). A role for epigenetics in hearing: establishment and maintenance of auditory specific gene expression patterns. Hear. Res. 233, 1-13. doi: 10.1016/j.heares.2007.07.002.
89. Rauschecker, J. P., Leaver, A. M., and Mühlau, M. (2010). Tuning out the noise: limbic-auditory interactions in tinnitus. Neuron 66, 819-826. doi: 10.1016/j.neuron.2010.04.032.
90. Requena, T., Cabrera, S., Martín-Sierra, C., Price, S. D., Lysakowski, A., and Lopez-Escamez, J. A. (2015). Identification of two novel mutations in FAM136A and DTNA genes in autosomal-dominant familial Meniere's disease. Hum. Mol. Genet. 24, 1119-1126. doi: 10.1093/hmg/ddu524.
91. Requena, T., Espinosa-Sanchez, J. M., Cabrera, S., Trinidad, G., Soto-Varela, A., Santos-Perez, S., et al. (2014). Familial clustering and genetic heterogeneity in Meniere's disease. Clin. Genet. 85, 245-252. doi: 10.1111/cge.12150.
92. Robinson, P. N., Krawitz, P., and Mundlos, S. (2011). Strategies for exome and genome sequence data analysis in disease-gene discovery projects. Clin. Genet. 80, 127-132. doi: 10.1111/j.1399-0004.2011.01713.x.
93. Samuels, D. C., Han, L., Li, J., Quanghu, S., Clark, T. A., Shyr, Y., et al. (2013). Finding the lost treasures in exome sequencing data. Trends Genet. 29, 593-599. doi: 10.1016/j.tig.2013.07.006.
94. Sand, P. G., Langguth, B., Itzhacki, J., Bauer, A., Geis, S., Cárdenas-Conejo, Z. E., et al. (2012a). Resequencing of the auxiliary GABA(B) receptor subunit gene KCTD12 in chronic tinnitus. Front. Syst. Neurosci. 6:41. doi: 10.3389/fnsys.2012.00041.
95. Sand, P. G., Langguth, B., and Kleinjung, T. (2011). Deep resequencing of the voltage-gated potassium channel subunit KCNE3 gene in chronic tinnitus. Behav. Brain Funct. 7:39. doi: 10.1186/1744-9081-7-39.
96. Sand, P. G., Langguth, B., Kleinjung, T., and Eichhammer, P. (2007). Genetics of chronic tinnitus. Prog. Brain Res. 166, 159-168. doi: 10.1016/S0079-6123(07)66014-2.
97. Sand, P. G., Langguth, B., Schecklmann, M., and Kleinjung, T. (2012b). GDNF and BDNF gene interplay in chronic tinnitus. Int. J. Mol. Epidemiol. Genet. 3, 245-251. doi: 10.1093/hmg/ddu524.
98. Sand, P. G., Luettich, A., Kleinjung, T., Hajak, G., and Langguth, B. (2010). An examination of KCNE1 mutations and common variants in chronic tinnitus. Genes 1, 23-37. doi: 10.3390/genes1010023.
99. Sanger, F., Nicklen, S., and Coulson, A. R. (1977). DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. U.S.A. 74, 5463-5467. doi: 10.1073/pnas.74.12.5463.
100. Schaette, R. (2014). Tinnitus in men, mice (as well as other rodents), and machines. Hear. Res. 311, 63-71. doi: 10.1016/j.heares.2013.12.004.
101. Schaette, R., and McAlpine, D. (2011). Tinnitus with a normal audiogram: physiological evidence for hidden hearing loss and computational model. J. Neurosci. 31, 13452-13457. doi: 10.1523/JNEUROSCI.2156-11.2011.
102. Schaette, R., Turtle, C., and Munro, K. J. (2012). Reversible induction of phantom auditory sensations through simulated unilateral hearing loss. PLoS ONE 7:e35238. doi: 10.1371/journal.pone.0035238.
103. Schecklmann, M., Landgrebe, M., Langguth, B., and Group, T. R. I. D. S. (2014). Phenotypic characteristics of hyperacusis in tinnitus. PLoS ONE 9:e86944. doi: 10.1371/journal.pone.0086944.
104. Schwartz, B., Wetzler, S., Swanson, A., and Sung, S. C. (2010). Subtyping of substance use disorders in a high-risk welfare-to-work sample: a latent class analysis. J. Subst. Abuse Treat. 38, 366-374. doi: 10.1016/j.jsat.2010.03.001.
105. Sellgren, C. M., Kegel, M. E., Bergen, S. E., Ekman, C. J., Olsson, S., Larsson, M., et al. (2015). A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder. Mol. Psychiatry. doi: 10.1038/mp.2015.186. [Epub ahead of print].
106. Shargorodsky, J., Curhan, G. C., and Farwell, W. R. (2010). Prevalence and characteristics of tinnitus among US adults. Am. J. Med. 123, 711-718. doi: 10.1016/j.amjmed.2010.02.015.
107. Shulman, A. (1995). A final common pathway for tinnitus-the medial temporal lobe system. Int. Tinnitus J. 1, 115-126.
108. Sindhusake, D., Mitchell, P., Newall, P., Golding, M., Rochtchina, E., and Rubin, G. (2003). Prevalence and characteristics of tinnitus in older adults: the blue mountains hearing Study. Int. J. Audiol. 42, 289-294. doi: 10.3109/14992020309078348.
109. Sobrinho, P. G., Oliveira, C. A., and Venosa, A. R. (2004). Long-term follow-up of tinnitus in patients with otosclerosis after stapes surgery. Int. Tinnitus J. 10, 197-201.
110. Stankiewicz, A. M., Swiergiel, A. H., and Lisowski, P. (2013). Epigenetics of stress adaptations in the brain. Brain Res. Bull. 98, 76-92. doi: 10.1016/j.brainresbull.2013.07.003.
111. Stenz, L., Zewdie, S., Laforge-Escarra, T., Prados, J., La Harpe, R., Dayer, A., et al. (2015). BDNF promoter I methylation correlates between post-mortem human peripheral and brain tissues. Neurosci. Res. 91, 1-7. doi: 10.1016/j.neures.2014.10.003.
112. Sztuka, A., Pospiech, L., Gawron, W., and Dudek, K. (2010). DPOAE in estimation of the function of the cochlea in tinnitus patients with normal hearing. Auris Nasus Larynx 37, 55-60. doi: 10.1016/j.anl.2009.05.001.
113. Tyler, R., Coelho, C., Tao, P., Ji, H., Noble, W., Gehringer, A., et al. (2008). Identifying tinnitus subgroups with cluster analysis. Am. J. Audiol. 17, S176-S184. doi: 10.1044/1059-0889(2008/07-0044).
114. Vaiserman, A. M. (2015). Epigenetic programming by early-life stress: evidence from human populations. Dev. Dyn. 244, 254-265. doi: 10.1002/dvdy.24211.
115. van Gendt, M. J., Boyen, K., de Kleine, E., Langers, D. R., and van Dijk, P. (2012). The relation between perception and brain activity in gaze-evoked tinnitus. J. Neurosci. 32, 17528-17539. doi: 10.1523/JNEUROSCI.2791-12.2012.
116. Veltman, J. A., and Brunner, H. G. (2012). De novo mutations in human genetic disease. Nat. Rev. Genet. 13, 565-575. doi: 10.1038/nrg3241.
117. Ward, J., Vella, C., Hoare, D. J., and Hall, D. A. (2015). Subtyping Somatic Tinnitus: a cross-sectional UK cohort study of demographic, clinical and audiological characteristics. PLoS ONE 10:e0126254. doi: 10.1371/journal.pone.0126254.
118. Wolber, L. E., Steves, C. J., Tsai, P. C., Deloukas, P., Spector, T. D., Bell, J. T., et al. (2014). Epigenome-wide DNA methylation in hearing ability: new mechanisms for an old problem. PLoS ONE 9:e105729. doi: 10.1371/journal.pone.0105729.
119. Yoshimura, H., Takumi, Y., Nishio, S. Y., Suzuki, N., Iwasa, Y., and Usami, S. (2014). Deafness gene expression patterns in the mouse cochlea found by microarray analysis. PLoS ONE 9:e92547. doi: 10.1371/journal.pone.0092547.
120. Zachriat, C., and Kröner-Herwig, B. (2004). Treating chronic tinnitus: comparison of cognitive-behavioural and habituation-based treatments. Cogn. Behav. Ther. 33, 187-198. doi: 10.1080/16506070410029568.
121. Zhang, X. (2014). Exome sequencing greatly expedites the progressive research of Mendelian diseases. Front. Med. 8:42-57. doi: 10.1007/s11684-014-0303-9.