In Search of Clues: Circulating Inflammatory Proteins and Unchanging Tinnitus

3rd January 2024 – by Kings College London

Professor Frances Williams’ Chronic Pain and Hearing Loss Research Group, part of our team at TwinsUK, has recently published another piece of the puzzle in the quest to understand and treat tinnitus. 

The large project – funded by Tinnitus UK as part of their Large Research Grants Programme – spanned Sweden and the UK, recruiting participants with tinnitus and matched controls firstly in over 1,000 participants in Sweden and then ran a replication of the study in over 1,000 twins from Twins UK. The primary objective of the research was to identify biomarkers for tinnitus.  

Co-author Max Freiden said:  

“It is difficult to establish biomarkers to detect or treat the disorder, because tinnitus is heterogeneous, indicating that various factors determine whether a person develops tinnitus.” 

Surprisingly, tinnitus shares several signs and symptoms with chronic pain. Neuroimaging suggests similar disturbances in the prefrontal cortex of the brain, leading to distorted interpretation of sensory inputs, such as sound.  A localised brain inflammatory response, detectable in the bloodstream, has been reported to occur with chronic pain. The team investigated whether inflammatory biomarkers could be found in people with tinnitus, hypothesising that chronic pain and constant tinnitus may be associated with neuroinflammation. 

Importantly, factors unrelated to hearing difficulties that affect inflammatory marker levels, such as age, sex, and body mass index, were accounted for. Tinnitus tends to be accompanied by stress, anxiety, depression, hypersensitivity to sound, face pain, and headache; however, none of these conditions were related to inflammatory marker levels. While a weak association of five inflammatory proteins was seen in the Swedish cohort, the finding was not replicated in the UK cohort, leading researchers to conclude there is a lack of association between plasma biomarkers and constant tinnitus. Other research has shown that biomarkers can be derived from electrophysiological measures, but this does not appear to be the case for blood biomarkers. 

Although the team didn’t find a tinnitus biomarker, negative results are considered progress and constitute an important aspect of directing future research and treatment. Such advancements are only possible with the generous research investments from charities like Tinnitus UK, and the important contribution of participants from TwinsUK and others who consent to research.  

Link to the article is HERE

Artificial Intelligence helps human radiologists: detecting intervertebral disc degeneration in MRI scans 

20th June 2023 – by Daliya Guemri

artificial intelligence

Researchers from TwinsUK have recently published a systematic review and meta-analysis examining the current efficacy of artificial intelligence (AI) machine learning applications that read MRI scans of degenerate discs. Working in the pain research team under Professor Frances Williams at King’s College London, researchers are motivated to glean the latest insights in developments to low back pain causes or treatment. Low back pain is the lead cause of disability globally and can fundamentally reduce patient quality of life. Intervertebral disc degeneration is a main cause of low back pain and Williams’ team is heavily invested in pioneering research into causes, diagnoses and treatments for the condition.  

Disc degeneration is a normal part of aging, however sometimes it is accompanied by disabling pain and interventions are required. This systematic review and meta-analysis specifically focused on machine learning (ML) algorithms that read lumbar magnetic resonance imaging (MRI) scans. Assessing disc degeneration is a time-consuming endeavour for radiologists, accurate machine learning algorithms that could fulfill this task, would represent a huge saving of work hours for health services across the globe. Fully exploiting AI technology could allow efficiency in identifying lumbar disc degeneration as well as other spinal conditions, and speed triaging patients for surgery or physiotherapy treatments.  

The systematic review found several studies with a computer science research focus that reported machine learning algorithms could do the job of radiologists, or that their approach could lead to diagnostic technology. Unfortunately, much of this software is not rigorously tested and most of the included studies had small numbers of participants. A systematic review and meta-analysis aim to the contribution of several small studies, however lack of replication (running the algorithm again in a totally new group of scans) was another stark omission from most of the included studies.   

In science, the best type of research is validated in different groups of participants and run multiple times. This should be a standard practice for medical treatments or tools. However they found that generally, these algorithms were not validated, and reports of added benefit to the assessment of disc degeneration were concluded perhaps prematurely.  

The technology is exciting as it does offer a real promise to the future of MRI reading and spinal assessments and ultimately better outcomes in patients with low back pain.  

Authors Roger Compte and Isabelle Granville Smith explained: 

We suggest future research should incorporate several machine learning approaches, such as adding semi- and un-supervised learning to supervised learning approaches. MRIs inherently contain vast quantities of information; of which the human eye is only capable of gleaning part. Designing machine learning algorithms that better take advantage of MRI data arrays may be a means to progress their reliability and accuracy to be comparable to and may one day surpass human radiologists.

Hear here! Hope for future treatments against hearing loss as researchers find 10 new genes and identify the affected ear structure

16th May 2022 – By Paz García

doctor and ear

Researchers led by Karolinska Institute, TwinsUK at King’s College London and Erasmus University have identified 10 new genes linked with hearing loss and located the part of the ear affected. 

The findings, published today in American Journal of Human Genetics, cast doubt on the dogma that age-related hearing impairment originates mainly from sensory hair cells and propose the stria vascularis in the cochlea as a new target for treatments to help people with hearing loss.  

Many people gradually lose some of their hearing ability as they get older, and an estimated 2.4 billion individuals will have some form of hearing loss by 2050. Age-related hearing impairment is a top contributor to years lived with disability and is also an important risk factor for dementia. 

The team studied genetic analyses previously carried out in centres around the world using samples from 723,266 people from 17 studies — including TwinsUK — who had clinically diagnosed or self-reported hearing impairment. The researchers identified 48 genes linked to hearing loss, including 10 new variants newly linked to hearing. 

Further analysis looking at mouse genetics indicated that age-related hearing loss is due to changes in the stria vascularis, a part of the cochlea in the ear, which is necessary for hearing. 

Co-main author Christopher R. Cederroth, Associate Professor at the Karolinska Institute, said: 

“It was hypothesized since the 1970s that the stria vascularis may play a role in hearing loss in humans, but the molecular evidence for this was missing until today.”  

Co-main author Frances Williams, Professor at King’s College London and TwinsUK researcher, said: 

“Our findings point to genes we could target for screening purposes, drug development and even gene therapy in the future. This study provides a solid foundation for ultimately improving therapies against hearing loss.” 

New project announced to tackle chronic pain

1st June 2021

Health Data Research UK, the Medical Research Council and Versus Arthritis have announced a new project to advance essential research into chronic pain.  

The project, called the Alleviate Hub, will bring together chronic pain data into one place.  

Researchers will be able to apply to use this data to help address complex questions about chronic pain, diagnosis, treatment and, to ultimately, improve the physical and mental wellbeing of those living with chronic pain.   

TwinsUK scientist and pain researcher Professor Frances Williams is a co-investigator on this project, which is led by the University of Dundee. 

The challenge 

Chronic pain is a major unmet global public health challenge that causes significant disability through conditions such as fibromyalgia, back pain, headaches and migraines. 

It is also a debilitating feature of long-term conditions including arthritis, cancer and dementia. 

To help address this challenge and improve the lives of people affected by pain conditions, better understanding of the mechanisms of pain and improved treatments are needed. 

The project 

The Alleviate Hub will maximise the value of chronic pain data from diverse sources, making the data Findable, Accessible, Interoperable and Reusable (‘FAIR’) for researchers and innovators to discover and request access to via the Health Data Research Innovation Gateway – a common entry point to discover and request access to an array of UK health-related datasets.  

The team of researchers will deliver world class health data infrastructure and services for pain research, guided by leading experts in pain research and in partnership with the NHS, Advanced Pain Discovery Platform consortia, people with lived experience of chronic pain, and industry.  

Professor Frances Williams said: 

“Chronic pain has a major impact on quality of life, and the condition is currently very challenging to treat. We hope that by making chronic pain data available in one place, we will be able to accelerate research into the condition and enable the development of effective treatments sooner for patients.” 

Study of 2,600 TwinsUK twins finds COVID-19 symptoms partly due to genes

27th April 2020

Genes are 50% responsible for the presentation of key symptoms of COVID-19 including fever, fatigue and loss of taste and smell, according to the latest data from TwinsUK researchers.

These results suggest that some people are more susceptible to COVID-19 infection than others because of their genetic makeup.

The genetic basis of this variation in response could provide researchers with important clues for developing treatments for COVID-19 and could help identify high-risk groups of people.

The team, led by Professor Frances Williams and Professor Tim Spector, analysed data logged on the COVID19 Symptom Tracker app which has been downloaded by more than 2 million people in the UK including 2,600 twins from TwinsUK.

15,000 twins take part in TwinsUK, which is the most clinically-detailed adult twin registry in the world. Identical and non-identical twins allow researchers to understand to what extent health and disease is affected by genes – nature – and the environment – nurture.

The team used information regarding the twins’ health, symptoms and level of contact with their co-twin to develop a model to understand how much genes influence symptom presentation in COVID-19.

Genes were almost 50% responsible for the development of symptoms of delirium, fever, fatigue, shortness of breath, diarrhoea and loss of taste and smell in individuals. The environment meanwhile was responsible for the development of other symptoms such as hoarse voice, cough, chest pain and abdominal pain.

Professor Frances Williams from TwinsUK said:

“I would like to say a big thank you to all our twins for logging their symptoms and health status regularly in the app. It’s because of their tremendous commitment to health research over the years that we are able to carry out this crucial research so quickly.”

Professor Tim Spector added:

“It’s essential that everybody keeps logging their health status in the app – even if you feel well. The data you provide enables us to carry out this urgent research to understand the behaviour and progression of the virus.”

The research paper with the full findings is available in non-peer reviewed archive format at the medRxiv site here.

Professor Frances Williams’ research celebrated by HRH The Duchess of Cornwall

Thursday 20th February – Paz Garcia

LONDON 18th Feb 2020. HRH The Duchess of Cornwall, hosted a reception for Versus Arthritis at Clarence House, London. Professor Frances Williams is eighth from the left. Photograph by Ian Jones.

Her Royal Highness The Duchess of Cornwall hosted a reception at Clarence House this week to celebrate the women leading the way in arthritis research – including our very own Professor Frances Williams.

Professor Williams’ work focuses on common conditions that cause high levels of disability in the general population, such as rheumatoid arthritis, back pain and other chronic pain conditions. She aims to understand how genetics, the environment and the microbiome – the millions of bacteria and other microbes that live in and on our bodies – are linked in the development of these conditions.

“I was delighted to be included in this event, particularly as Versus Arthritis recently agreed to fund our Spine Microbiome project. In this novel study we will collect and examine intervertebral discs which are removed at spine operations for back pain. We will use new microbiome techniques to answer the question of whether some bugs get into the disc and bones and cause back pain.”

– Professor Frances Williams

Arthritis charity Versus Arthritis (previously Arthritis Research UK and Arthritis Research Campaign) has supported Professor Williams’ throughout her career, as well as the creation of TwinsUK.

Hope for hearing loss

26th September 2019 – by Paz Garcia

Hand holding a hearing aid against a green background

A new study of over 250,000 volunteers has identified 44 new genes linked to age-related hearing loss.

A third of people are affected by some degree of hearing loss by the age of 65, which can lead to social isolation and disability.

Despite being such a common sensory impairment, hearing aids are the only treatment available and not much is known about the genes behind the condition.

These findings will help researchers understand how hearing loss develops and so help us find ways to treat and prevent the condition.

Professor Frances Williams, who led the collaborative research using data from UK Biobank, TwinsUK and ELSA among others, explained: 

“We now know that very many genes are involved in the loss of hearing ability as we age. This study has identified genes that we know already cause deafness in children, but it has also revealed lots of additional genes which point to new biological pathways.”

The study is the largest genetic analysis conducted to date of people who report problems with their hearing.

The work was from a joint project involving King’s College London and University College London.

What did they do?

The team wanted to identify the genetic component of adult hearing loss in the UK so that we can understand better how the condition develops as we age.

The researchers analysed the genetic data and questionnaire responses about hearing in over 250,000 participants of the UK Biobank aged 40-69 years to see which genes were associated with people who had self-reported hearing problems.

The team identified 44 new genes linked with age-related hearing loss of which 34 have not been linked to any form of hearing loss previously.

The researchers then checked their findings by studying TwinsUK and the English Longitudinal Study of Ageing.

What does this mean?

These finding will help researchers untangle the sequence of events that lead to hearing impairment as we age. Future research will investigate the biological hearing pathways influenced by these genes.

This will help us to identify possible targets for new therapies to treat and potentially prevent or delay hearing loss with age.

Wells et al., GWAS Identifies 44 Independent Associated Genomic Loci for Self-Reported Adult Hearing Difficulty in UK Biobank, The American Journal of Human Genetics (2019).

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