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      Association of Genetic vs Environmental Factors in Swedish Adoptees With Clinically Significant Tinnitus

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          Abstract

          This study uses Swedish national registry data to assess the association between genetic vs environmental factors and risk of tinnitus among adoptees.

          Key Points

          Question

          Is clinically significant tinnitus associated with genetic factors?

          Findings

          In this study of national registry data from 11 060 adoptees, 19 015 adoptive parents, and 17 025 biological parents, a heritability of 32% and no association of shared environment with the transmission of tinnitus were found.

          Meaning

          The present study suggests that genetic factors are associated with the familial clustering of severe tinnitus.

          Abstract

          Importance

          No effective treatments are currently available for severe tinnitus, which affects 1% of the population and lowers the quality of life. The factors that contribute to the transition from mild to severe tinnitus are poorly known. Before performing genetic analyses and determining the mechanisms involved in the development of severe tinnitus, its heritability needs to be determined.

          Objectives

          To examine whether clinically significant tinnitus is associated with genetic factors and to evaluate the genetic risk in the transmission of tinnitus using adoptees.

          Design, Setting, and Participants

          Data from adoptees and their biological and adoptive parents from Swedish nationwide registers were collected from January 1, 1964, to December 31, 2015, and used to separate genetic from environmental factors in familial clustering. In all, 11 060 adoptees, 19 015 adoptive parents, and 17 025 biological parents were investigated. The study used a cohort design and a case-control approach to study genetic and nongenetic factors in tinnitus among adoptees.

          Main Outcomes and Measures

          The primary outcome was odds ratio (OR) of tinnitus in adoptees with at least 1 affected biological parent compared with adoptees without any affected biological parent using logistic regression. The secondary outcome was OR in adoptees with at least 1 affected adoptive parent compared with adoptees without any affected adoptive parent.

          Results

          A total of 1029 patients (440 [42.8%] male; mean [SD] age, 62 [14] years) with tinnitus were identified. The prevalence of diagnosed tinnitus was 2.2%. The OR for tinnitus was 2.22 for adoptees (95% CI, 1.03-4.81) of biological parents diagnosed with tinnitus, whereas the OR was 1.00 (95% CI, 0.43-2.32) for adoptees from adoptive parents diagnosed with tinnitus. Mean (SE) heritability determined using tetrachoric correlations was 31% (14%).

          Conclusions and Relevance

          The findings suggest that genetic factors are associated with the familial clustering of clinically significant tinnitus with no shared-environment association, revealing that the transition from negligible to severe tinnitus may be associated with genetic factors. These findings may provide insight for future genetic analyses that focus on severe tinnitus.

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          Most cited references38

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          The inheritance of liability to certain diseases, estimated from the incidence among relatives

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            The Swedish Multi-generation Register.

            The Swedish Multi-generation Register consists of data of more than nine million individuals, with information available on mothers in 97% and on fathers in 95% of index persons. Index persons are confined to those born from 1932 onwards and those alive on January 1, 1961. This register is a unique resource but is still underutilized.
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              Dysregulation of limbic and auditory networks in tinnitus.

              Tinnitus is a common disorder characterized by ringing in the ear in the absence of sound. Converging evidence suggests that tinnitus pathophysiology involves damage to peripheral and/or central auditory pathways. However, whether auditory system dysfunction is sufficient to explain chronic tinnitus is unclear, especially in light of evidence implicating other networks, including the limbic system. Using functional magnetic resonance imaging and voxel-based morphometry, we assessed tinnitus-related functional and anatomical anomalies in auditory and limbic networks. Moderate hyperactivity was present in the primary and posterior auditory cortices of tinnitus patients. However, the nucleus accumbens exhibited the greatest degree of hyperactivity, specifically to sounds frequency-matched to patients' tinnitus. Complementary structural differences were identified in ventromedial prefrontal cortex, another limbic structure heavily connected to the nucleus accumbens. Furthermore, tinnitus-related anomalies were intercorrelated in the two limbic regions and between limbic and primary auditory areas, indicating the importance of auditory-limbic interactions in tinnitus. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                JAMA Otolaryngol Head Neck Surg
                JAMA Otolaryngol Head Neck Surg
                JAMA Otolaryngol Head Neck Surg
                JAMA Otolaryngology-- Head & Neck Surgery
                American Medical Association
                2168-6181
                2168-619X
                17 January 2019
                March 2019
                17 January 2019
                : 145
                : 3
                : 222-229
                Affiliations
                [1 ]Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
                [2 ]Centre for Primary Health Care Research, Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden
                [3 ]Hörsel-och Balanskliniken, Karolinska Universitetssjukhuset, Stockholm, Sweden
                Author notes
                Article Information
                Accepted for Publication: November 9, 2019.
                Published Online: January 17, 2019. doi:10.1001/jamaoto.2018.3852
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Cederroth CR et al. JAMA Otolaryngology.
                Corresponding Author: Christopher R. Cederroth, PhD, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Solnavägen 9, Stockholm 171 77, Sweden ( christopher.cederroth@ 123456ki.se ).
                Author Contributions: Drs PirouziFard and Zöller had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Cederroth, PirouziFard, Trpchevska, Idrizbegovic, J. Sundquist, K. Sundquist, Zöller.
                Acquisition, analysis, or interpretation of data: Cederroth, PirouziFard, Canlon, K. Sundquist, Zöller.
                Drafting of the manuscript: Cederroth, PirouziFard, Trpchevska, Idrizbegovic, Canlon.
                Critical revision of the manuscript for important intellectual content: Cederroth, PirouziFard, Trpchevska, Canlon, J. Sundquist, K. Sundquist, Zöller.
                Statistical analysis: PirouziFard, Canlon, Zöller.
                Obtained funding: Cederroth, Canlon, J. Sundquist, K. Sundquist, Zöller.
                Administrative, technical, or material support: Trpchevska, J. Sundquist, K. Sundquist.
                Supervision: Cederroth, K. Sundquist, Zöller.
                Conflict of Interest Disclosures: Dr Cederroth reported having received consulting fees from Sensorion Pharmaceuticals. No other disclosures were reported.
                Funding/Support: This study was supported by grant K2014 99X 22478 01 3 from the Swedish Medical Research Council (Dr Canlon), Karolinska Institute (Dr Cederroth), Tysta Skolan (Drs Cederroth and Canlon), grant SLS-779681 from Svenska Läkaresällskapet (Dr Cederroth), grant 503 from Hörselforskningsfonden (Dr Cederroth), Marie Skłodowska-Curie grant agreement 72204655 from the European Union’s Horizon 2020 research and innovation program (Dr Cederroth), Decibel Therapeutics Inc (Dr Cederroth), Avtal om Läkarutbildning och forskning funding (Drs J. Sundquist, K. Sundquist, and Zöller), and the Swedish Heart-Lung Foundation (Dr Zöller).
                Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Article
                ooi180103
                10.1001/jamaoto.2018.3852
                6439751
                30653224
                b2f304c1-d7ec-4509-897f-434d096e8380
                Copyright 2019 Cederroth CR et al. JAMA Otolaryngology.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 14 July 2018
                : 4 October 2018
                : 9 November 2018
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