Prevalence, Incidence Proportion, and Heritability for Tinnitus: A Longitudinal Twin Study

http://journals.lww.com/ear-hearing...Incidence_Proportion,_and_Heritability.3.aspx

Objectives: The purpose of this longitudinal twin study was to explore the effect of tinnitus on hearing thresholds and threshold shifts over two decades and to investigate the genetic contribution to tinnitus in a male twin cohort (n = 1114 at baseline and 583 at follow-up). The hypothesis was that participants with faster hearing deterioration had a higher risk for developing tinnitus and there is an underlying role of genetic influences on tinnitus.

Conclusions: Our hypotheses were confirmed: The fastest hearing deterioration occurred for new tinnitus cases. A moderate genetic influence for tinnitus was confirmed.

 

Heritability and Genetics Contribution to Tinnitus
Jose A. Lopez-Escamez, Sana Amanat

Tinnitus is the perception of sound in the absence of an external source. Genetic studies on families, twins, and adoptees cohorts have been conducted supporting tinnitus heritability, with higher heritability in men with bilateral tinnitus at any age, and young women with bilateral tinnitus, but not in unilateral tinnitus. The condition is associated with several comorbidities such as hearing loss, Meniere disease, sleep disorders, depression, and migraine and may lead toward suicidal attempts in extreme cases. Several studies have reported few regulatory allelic variants in candidate genes and pathways associated with tinnitus development, but replication studies are needed to validate them.

Behind a paywall.

 

The biggest mystery is to figure out why some people develop tinnitus and phantom syndromes and why others don't. As well as why some cases fade and others don't.


While scientist tackle the hard questions, ENT's are still in the realm of tinnitus and hearing loss are unrelated.

 

Just my own experience:

Too much damage = no fading.

 

A New Buzz for Tinnitus—It’s in the Genes!
Christopher R. Cederroth, PhD; Natalia Trpchevska, MD; Berthold Langguth, MD, PhD

Spoiler

“Does tinnitus run in your family?” Seldom is that question asked by clinicians to their patients with tinnitus, but why would they ask? Audiologists and ear, nose, and throat specialists see patients with tinnitus in association with either conductive or sensorineural hearing loss, which has led to the clinical dogma that tinnitus is secondary and by definition a symptom arising from the hearing disorder. However, tinnitus may occur in absence of any detectable auditory dysfunction, most particularly in young individuals, which raises the question on the origins of these more sporadic cases of phantom percept.

In this issue of JAMA Otolaryngology–Head & Neck Surgery, Clifford et al1 present the first evidence in a genome-wide association study (GWAS) of 3 loci and 8 genes associated with tinnitus and replicated in 2 independent large cohorts of European ancestry: the UK Biobank and the Million Veterans Program. These findings go against the preconceived notion that tinnitus is purely a symptom and demonstrate that, at least in part, its neurological basis lies in the genes. A GWAS is the primary step in establishing the connection between genes and a trait by investigating the level of genetic variation between cases and controls. Thus, rather than looking at all the sequences from the entire genome, Clifford et al1 looked at specific sites across the whole genome, termed single-nucleotide variants (SNVs), where variations are expected to happen.

A number of variants showed up consistently among individuals with tinnitus but not among those without tinnitus. Heritability of SNVs explained 6.3% of the variation; in other words, the identified SNVs explain nearly 6% of the trait. Including hearing difficulties as a covariate reduced tinnitus heritability by 18.8% to 35.6%, which reinforces the paradigm-shifting concept that not all tinnitus cases depend on hearing loss. With more than 1 gene being significantly associated with tinnitus, tinnitus can be defined as a polygenic disorder.

Although these findings clearly demonstrate that tinnitus has a heritable component, they also indicate the importance of environmental factors in determining the full manifestation of tinnitus. Altogether, these features define tinnitus as a complex disorder, as opposed to rare mendelian disorders, wherein multiple genes and environmental factors interact together to generate a phenotype.

Novel Risk Loci in Tinnitus and Causal Inference With Neuropsychiatric Disorders Among Adults of European Ancestry
Royce E. Clifford, MD, MPH; Adam X. Maihofer, MS; Murray B. Stein, MD, MPH; et al

Spoiler

Importance: Tinnitus affects at least 16 million US adults, but its pathophysiology is complicated, and treatment options remain limited. A heritable component has been identified in family and twin studies; however, no large-scale genome-wide association studies (GWAS) have been accomplished.

Objective: To identify genetic risk loci associated with tinnitus, determine genetic correlations, and infer possible relationships of tinnitus with hearing loss and neuropsychiatric disorders and traits.

Design, Setting, and Participants: A GWAS of self-reported tinnitus was performed in the UK Biobank (UKB) cohort using a linear mixed-model method implemented in BOLT-LMM (linear mixed model). Replication of significant findings was sought in the nonoverlapping US Million Veteran Program (MVP) cohort. A total of 172 995 UKB (discovery) and 260 832 MVP (replication) participants of European ancestry with self-report regarding tinnitus and hearing loss underwent genomic analysis. Linkage-disequilibrium score regression and mendelian randomization were performed between tinnitus and hearing loss and neuropsychiatric disorders. Data from the UKB were acquired and analyzed from September 24, 2018, to December 13, 2019. Data acquisition for the MVP cohort was completed July 22, 2019. Data analysis for both cohorts was completed on February 11, 2020.

Main Outcomes and Measures: Estimates of single nucleotide variation (SNV)–based heritability for tinnitus, identification of genetic risk loci and genes, functional mapping, and replication were performed. Genetic association and inferred causality of tinnitus compared with hearing loss and neuropsychiatric disorders and traits were analyzed.

Results: Of 172 995 UKB participants (53.7% female; mean [SD], 58.0 [8.2] years), 155 395 unrelated participants underwent SNV-based heritability analyses across a range of tinnitus phenotype definitions that explained approximately 6% of the heritability. The GWAS based on the most heritable model in the full UKB cohort identified 6 genome-wide significant loci and 27 genes in gene-based analyses, with replication of 3 of 6 loci and 8 of 27 genes in 260 832 MVP cohort participants (92.8% men; mean [SD] age, 63.8 [13.2] years). Mendelian randomization indicated that major depressive disorder had a permissive effect (β = 0.133; P = .003) and years of education had a protective effect (β = −0.322, P = <.001) on tinnitus, whereas tinnitus and hearing loss inferred a bidirectional association (β = 0.072, P = .001 and β = 1.546, P = <.001, respectively).

Conclusions and Relevance: This large GWAS characterizes the genetic architecture of tinnitus, demonstrating modest but significant heritability and a polygenic profile with multiple significant risk loci and genes. Genetic correlation and inferred causation between tinnitus and major depressive disorder, educational level, and hearing impairment were identified, consistent with clinical and neuroimaging evidence. These findings may guide gene-based diagnostic and therapeutic approaches to this pervasive disorder.

"These findings go against the preconceived notion that tinnitus is purely a symptom and demonstrate that, at least in part, its neurological basis lies in the genes."

 

Fascinating study. The history of our ailment makes for very compelling reading and the more knowledge we can gain on this, the better. I recall the leader of our tinnitus group back in the 90s [sorry, no link] mentioning that the incidence of tinnitus among members of the orchestra -- or was it those of the orchestra who came down with tinnitus quickest? -- was not the drummer, not the piana player, it was the piccolo player. For the musically uninitiated the piccolo is a very high-pitched flute.

Any econometric study, should also include profession/job as a co-factor in my humble opinion.