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Article ; Online: Genetic analysis of probable sleep bruxism and its associations with clinical and behavioral traits.

Strausz, Tommi / Strausz, Satu / Palotie, Tuula / Ahlberg, Jari / Ollila, Hanna M

2023 Volume 46, Issue 10

Abstract: Study objectives: Sleep bruxism (SB) can cause damage on teeth, headache and severe pain affecting both sleep and daily functioning. Yet despite the growing interest into bruxism, the underlying clinically relevant biological mechanisms remain ... ...

Abstract	Study objectives: Sleep bruxism (SB) can cause damage on teeth, headache and severe pain affecting both sleep and daily functioning. Yet despite the growing interest into bruxism, the underlying clinically relevant biological mechanisms remain unresolved. The aim of our study was to understand biological mechanisms and clinical correlates of SB including previously reported disease associations. Methods: We used data from the FinnGen release R9 (N = 377 277 individuals) that are linked with Finnish hospital and primary care registries. We identified 12 297 (3.26%) individuals with International Classification of Diseases (ICD)-10 codes used for SB. In addition, we used logistic regression to examine the association between probable SB and its clinically diagnosed risk factors and comorbidities using ICD-10 codes. Furthermore, we examined medication purchases using prescription registry. Finally, we performed the first genome-wide association analysis for probable SB and computed genetic correlations using questionnaire, lifestyle, and clinical traits. Results: The genome-wide association analysis revealed one significant association: rs10193179 intronic to Myosin IIIB (MYO3B) gene. In addition, we observed phenotypic associations and high genetic correlations with pain diagnoses, sleep apnea, reflux disease, upper respiratory diseases, psychiatric traits, and also their related medications such as antidepressants and sleep medication (p < 1e-4 for each trait). Conclusions: Our study provides a large-scale genetic framework to understand risk factors for SB and suggests potential biological mechanisms. Furthermore, our work strengthens the important earlier work that highlights SB as a trait that is associated with multiple axes of health. As part of this study, we provide genome-wide summary statistics that we hope will be useful for the scientific community studying SB.
Language	English
Publishing date	2023-05-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	424441-2
ISSN	1550-9109 ; 0161-8105
ISSN (online)	1550-9109
ISSN	0161-8105
DOI	10.1093/sleep/zsad107
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Zs.A 1475: Show issues

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Article ; Online: Genetic Analysis of Obstructive Sleep Apnea and Its Relationship with Severe COVID-19.

Strausz, Satu / Agafonova, Elizabete / Tiullinen, Varvara / Kiiskinen, Tuomo / Broberg, Martin / Ruotsalainen, Sanni E / Koskela, Jukka / Bachour, Adel / Sofer, Tamar / Gottlieb, Daniel J / Palotie, Aarno / Palotie, Tuula / Ripatti, Samuli / Ollila, Hanna M

Annals of the American Thoracic Society

2024 Volume 21, Issue 6, Page(s) 961–970

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Humans ; COVID-19/complications ; COVID-19/genetics ; COVID-19/epidemiology ; Sleep Apnea, Obstructive/genetics ; Sleep Apnea, Obstructive/epidemiology ; Sleep Apnea, Obstructive/complications ; Male ; Female ; Genome-Wide Association Study ; Middle Aged ; Mendelian Randomization Analysis ; SARS-CoV-2/genetics ; Risk Factors ; Aged ; Genetic Predisposition to Disease ; Body Mass Index ; Hospitalization/statistics & numerical data ; Severity of Illness Index ; Finland/epidemiology ; Polymorphism, Single Nucleotide ; Adult
Language	English
Publishing date	2024-02-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2717461-X
ISSN	2325-6621 ; 1943-5665 ; 2325-6621
ISSN (online)	2325-6621 ; 1943-5665
ISSN	2325-6621
DOI	10.1513/AnnalsATS.202303-215OC
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Zs.A 5828: Show issues

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Article ; Online: Large registry-based analysis of genetic predisposition to tuberculosis identifies genetic risk factors at HLA.

Tervi, Anniina / Junna, Nella / Broberg, Martin / Jones, Samuel E / Strausz, Satu / Kreivi, Hanna-Riikka / Heckman, Caroline A / Ollila, Hanna M

Human molecular genetics

2022 Volume 32, Issue 1, Page(s) 161–171

Abstract: Tuberculosis is a significant public health concern resulting in the death of over 1 million individuals each year worldwide. While treatment options and vaccines exist, a substantial number of infections still remain untreated or are caused by treatment ...

Abstract	Tuberculosis is a significant public health concern resulting in the death of over 1 million individuals each year worldwide. While treatment options and vaccines exist, a substantial number of infections still remain untreated or are caused by treatment resistant strains. Therefore, it is important to identify mechanisms that contribute to risk and prognosis of tuberculosis as this may provide tools to understand disease mechanisms and provide novel treatment options for those with severe infection. Our goal was to identify genetic risk factors that contribute to the risk of tuberculosis and to understand biological mechanisms and causality behind the risk of tuberculosis. A total of 1895 individuals in the FinnGen study had International Classification of Diseases-based tuberculosis diagnosis. Genome-wide association study analysis identified genetic variants with statistically significant association with tuberculosis at the human leukocyte antigen (HLA) region (P < 5e-8). Fine mapping of the HLA association provided evidence for one protective haplotype tagged by HLA DQB105:01 (P = 1.82E-06, OR = 0.81 [CI 95% 0.74-0.88]), and predisposing alleles tagged by HLA DRB113:02 (P = 0.00011, OR = 1.35 [CI 95% 1.16-1.57]). Furthermore, genetic correlation analysis showed association with earlier reported risk factors including smoking (P < 0.05). Mendelian randomization supported smoking as a risk factor for tuberculosis (inverse-variance weighted P < 0.05, OR = 1.83 [CI 95% 1.15-2.93]) with no significant evidence of pleiotropy. Our findings indicate that specific HLA alleles associate with the risk of tuberculosis. In addition, lifestyle risk factors such as smoking contribute to the risk of developing tuberculosis.
MeSH term(s)	Humans ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Tuberculosis/genetics ; HLA-DQ beta-Chains/genetics ; HLA-DRB1 Chains/genetics ; Haplotypes/genetics ; Risk Factors ; Alleles ; Gene Frequency
Chemical Substances	HLA-DQ beta-Chains ; HLA-DRB1 Chains
Language	English
Publishing date	2022-08-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddac212
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Zs.A 3469: Show issues

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Article ; Online: The public health impact of poor sleep on severe COVID-19, influenza and upper respiratory infections.

Jones, Samuel E / Maisha, Fahrisa I / Strausz, Satu J / Lammi, Vilma / Cade, Brian E / Tervi, Anniina / Helaakoski, Viola / Broberg, Martin E / Lane, Jacqueline M / Redline, Susan / Saxena, Richa / Ollila, Hanna M

EBioMedicine

2023 Volume 93, Page(s) 104630

Abstract: Background: Poor sleep is associated with an increased risk of infections and all-cause mortality but the causal direction between poor sleep and respiratory infections has remained unclear. We examined if poor sleep contributes as a causal risk factor ... ...

Abstract	Background: Poor sleep is associated with an increased risk of infections and all-cause mortality but the causal direction between poor sleep and respiratory infections has remained unclear. We examined if poor sleep contributes as a causal risk factor to respiratory infections. Methods: We used data on insomnia, influenza and upper respiratory infections (URIs) from primary care and hospital records in the UK Biobank (N ≈ 231,000) and FinnGen (N ≈ 392,000). We computed logistic regression to assess association between poor sleep and infections, disease free survival hazard ratios, and performed Mendelian randomization analyses to assess causality. Findings: Utilizing 23 years of registry data and follow-up, we discovered that insomnia diagnosis associated with increased risk for infections (FinnGen influenza Cox's proportional hazard (CPH) HR = 4.34 [3.90, 4.83], P = 4.16 × 10 Interpretation: Our findings indicate that chronic poor sleep is a causal risk factor for contracting respiratory infections, and in addition contributes to the severity of respiratory infections. These findings highlight the role of sleep in maintaining sufficient immune response against pathogens. Funding: Instrumentarium Science Foundation, Academy of Finland, Signe and Ane Gyllenberg Foundation, National Institutes of Health.
MeSH term(s)	Humans ; Influenza, Human/complications ; Influenza, Human/epidemiology ; Sleep Initiation and Maintenance Disorders ; Public Health ; COVID-19/complications ; COVID-19/epidemiology ; Respiratory Tract Infections/complications ; Respiratory Tract Infections/epidemiology ; Sleep ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2023-06-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104630
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Zs.A 7090: Show issues

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Article ; Online: SCGB1D2 inhibits growth of Borrelia burgdorferi and affects susceptibility to Lyme disease.

Nature communications

2024 Volume 15, Issue 1, Page(s) 2041

Abstract: Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data from FinnGen and Estonian Biobank, we ... ...

Abstract	Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data from FinnGen and Estonian Biobank, we identify two previously known variants and an unknown common missense variant at the gene encoding for Secretoglobin family 1D member 2 (SCGB1D2) protein that increases the susceptibility for Lyme disease. Using live Borrelia burgdorferi (Bb) we find that recombinant reference SCGB1D2 protein inhibits the growth of Bb in vitro more efficiently than the recombinant protein with SCGB1D2 P53L deleterious missense variant. Finally, using an in vivo murine infection model we show that recombinant SCGB1D2 prevents infection by Borrelia in vivo. Together, these data suggest that SCGB1D2 is a host defense factor present in the skin, sweat, and other secretions which protects against Bb infection and opens an exciting therapeutic avenue for Lyme disease.
MeSH term(s)	Mice ; Animals ; Humans ; Borrelia burgdorferi/genetics ; Lyme Disease/microbiology ; Ixodes/microbiology ; Secretoglobins
Chemical Substances	SCGB1D2 protein, human ; Secretoglobins
Language	English
Publishing date	2024-03-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45983-9
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Article: The public health impact of poor sleep on severe COVID-19, influenza and upper respiratory infections.

Jones, Samuel E / Maisha, Fahrisa I / Strausz, Satu J / Cade, Brian E / Tervi, Anniina M / Helaakoski, Viola / Broberg, Martin E / Lammi, Vilma / Lane, Jacqueline M / Redline, Susan / Saxena, Richa / Ollila, Hanna M

medRxiv : the preprint server for health sciences

2022

Abstract: Background: Poor sleep is associated with an increased risk of infections and all-cause mortality, and acute sleep loss and disruption have been linked with inflammation and poorer immune control. Previous studies, however, have been unable to evidence ... ...

Abstract	Background: Poor sleep is associated with an increased risk of infections and all-cause mortality, and acute sleep loss and disruption have been linked with inflammation and poorer immune control. Previous studies, however, have been unable to evidence causality between the chronic effects of poor sleep and respiratory infection risk. In light of the ongoing COVID-19 pandemic and potential future disease outbreaks, understanding the risk factors for these infections is of great importance. Aim: Our goal was to understand if chronic poor sleep could be identified as a causal risk factor for respiratory infections including influenza, upper respiratory infections and COVID-19. Methods: We used population cohorts from the UK Biobank (N ≈ 231,000) and FinnGen (N ≈ 327,000) with ICD-10 based electronic health records and obtained diagnoses of insomnia, influenza and upper respiratory infections (URIs) from primary care and hospital settings. We computed logistic regression to assess association between poor sleep and infections, disease free survival hazard ratios, and used summary statistics from genome-wide association studies of insomnia, influenza, URI and COVID-19 to perform Mendelian randomization analyses and assess causality. Findings: Utilizing 23 years of registry data and follow-up, we saw that insomnia diagnosis associated with increased risk for infections in FinnGen and in UK Biobank (FinnGen influenza HR = 5.32 [4.09, 6.92], P = 1.02×10 Conclusions: Our findings indicate that chronic poor sleep is a causal risk factor for contracting respiratory infections, and in addition contributes to the severity of respiratory infections. These findings highlight the role of sleep in maintaining sufficient immune response against pathogens as suggested by earlier work. As the current COVID-19 pandemic has increased the number of people suffering from poor sleep, safe interventions such as sleep management and treating individuals with insomnia could be promoted to reduce infections and save lives.
Language	English
Publishing date	2022-02-17
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.02.16.22271055
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Article ; Online: Sleep apnoea is a risk factor for severe COVID-19.

Strausz, Satu / Kiiskinen, Tuomo / Broberg, Martin / Ruotsalainen, Sanni / Koskela, Jukka / Bachour, Adel / Palotie, Aarno / Palotie, Tuula / Ripatti, Samuli / Ollila, Hanna M

BMJ open respiratory research

2021 Volume 8, Issue 1

Abstract: Background: Obstructive sleep apnoea (OSA) is associated with higher body mass index (BMI), diabetes, older age and male gender, which are all risk factors for severe COVID-19.We aimed to study if OSA is an independent risk factor for COVID-19 infection ...

Abstract	Background: Obstructive sleep apnoea (OSA) is associated with higher body mass index (BMI), diabetes, older age and male gender, which are all risk factors for severe COVID-19.We aimed to study if OSA is an independent risk factor for COVID-19 infection or for severe COVID-19. Methods: OSA diagnosis and COVID-19 infection were extracted from the hospital discharge, causes of death and infectious diseases registries in individuals who participated in the FinnGen study (n=260 405). Severe COVID-19 was defined as COVID-19 requiring hospitalisation. Multivariate logistic regression model was used to examine association. Comorbidities for either COVID-19 or OSA were selected as covariates. We performed a meta-analysis with previous studies. Results: We identified 445 individuals with COVID-19, and 38 (8.5%) of them with OSA of whom 19 out of 91 (20.9%) were hospitalised. OSA associated with COVID-19 hospitalisation independent from age, sex, BMI and comorbidities (p-unadjusted=5.13×10 Conclusion: Risk for contracting COVID-19 was the same for patients with OSA and those without OSA. In contrast, among COVID-19 positive patients, OSA was associated with higher risk for hospitalisation. Our findings are in line with earlier works and suggest OSA as an independent risk factor for severe COVID-19.
MeSH term(s)	Aged ; COVID-19/epidemiology ; Comorbidity ; Female ; Finland/epidemiology ; Humans ; Male ; Middle Aged ; Registries ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Sleep Apnea, Obstructive/epidemiology
Language	English
Publishing date	2021-01-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2736454-9
ISSN	2052-4439 ; 2052-4439
ISSN (online)	2052-4439
ISSN	2052-4439
DOI	10.1136/bmjresp-2020-000845
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Article ; Online: The public health impact of poor sleep on severe COVID-19, influenza and upper respiratory infections

Jones, Samuel E. / Maisha, Fahrisa I. / Strausz, Satu J. / Cade, Brian E. / Tervi, Anniina M. / Helaakoski, Viola / Broberg, Martin E. / Lammi, Vilma / FinnGen / Lane, Jacqueline M. / Redline, Susan / Saxena, Richa / Ollila, Hanna M.

medRxiv

Abstract: ... Background ... Poor sleep is associated with an increased risk of infections and all-cause mortality, and acute sleep loss and disruption have been linked with inflammation and poorer immune control. Previous studies, however, have been unable to ... ...

Abstract	Background Poor sleep is associated with an increased risk of infections and all-cause mortality, and acute sleep loss and disruption have been linked with inflammation and poorer immune control. Previous studies, however, have been unable to evidence causality between the chronic effects of poor sleep and respiratory infection risk. In light of the ongoing COVID-19 pandemic and potential future disease outbreaks, understanding the risk factors for these infections is of great importance. Aim Our goal was to understand if chronic poor sleep could be identified as a causal risk factor for respiratory infections including influenza, upper respiratory infections and COVID-19. Methods We used population cohorts from the UK Biobank (N ≈ 231,000) and FinnGen (N ≈ 327,000) with ICD-10 based electronic health records and obtained diagnoses of insomnia, influenza and upper respiratory infections (URIs) from primary care and hospital settings. We computed logistic regression to assess association between poor sleep and infections, disease free survival hazard ratios, and used summary statistics from genome-wide association studies of insomnia, influenza, URI and COVID-19 to perform Mendelian randomization analyses and assess causality. Findings Utilizing 23 years of registry data and follow-up, we saw that insomnia diagnosis associated with increased risk for infections in FinnGen and in UK Biobank (FinnGen influenza HR = 5.32 [4.09, 6.92], P = 1.02×10<sup>-35</sup>, UK Biobank influenza HR = 1.54 [1.37, 1.73], P = 2.49×10<sup>-13</sup>). Mendelian randomization indicated that insomnia causally predisposed to influenza (OR = 1.59, P = 6.23×10<sup>-4</sup>), upper respiratory infections (OR = 1.71, P = 7.60×10<sup>-13</sup>), COVID-19 infection (OR = 1.08, P = 0.037) and risk of hospitalization from COVID-19 (OR = 1.47, P = 4.96×10<sup>-5</sup>). Conclusions Our findings indicate that chronic poor sleep is a causal risk factor for contracting respiratory infections, and in addition contributes to the severity of respiratory infections. These findings highlight the role of sleep in maintaining sufficient immune response against pathogens as suggested by earlier work. As the current COVID-19 pandemic has increased the number of people suffering from poor sleep, safe interventions such as sleep management and treating individuals with insomnia could be promoted to reduce infections and save lives.
Keywords	covid19
Language	English
Publishing date	2022-02-17
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2022.02.16.22271055
Database	COVID19

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Article ; Online: Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health.

The European respiratory journal

2021 Volume 57, Issue 5

Abstract: There is currently limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). We aimed to identify genetic loci associated with OSA risk, and to test if OSA and its comorbidities share a common genetic background.We conducted the ... ...

Abstract	There is currently limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). We aimed to identify genetic loci associated with OSA risk, and to test if OSA and its comorbidities share a common genetic background.We conducted the first large-scale genome-wide association study of OSA using the FinnGen study (217 955 individuals) with 16 761 OSA patients identified using nationwide health registries.We estimated 0.08 (95% CI 0.06-0.11) heritability and identified five loci associated with OSA (p<5.0×10
MeSH term(s)	Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; Body Mass Index ; Diabetes Mellitus, Type 2 ; Genome-Wide Association Study ; Humans ; Hypertension ; Risk Factors ; Sleep Apnea, Obstructive
Chemical Substances	Alpha-Ketoglutarate-Dependent Dioxygenase FTO (EC 1.14.11.33) ; FTO protein, human (EC 1.14.11.33)
Language	English
Publishing date	2021-05-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.03091-2020
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Article ; Online: Obstructive sleep apnoea and the risk for coronary heart disease and type 2 diabetes: a longitudinal population-based study in Finland.

Strausz, Satu / Havulinna, Aki S / Tuomi, Tiinamaija / Bachour, Adel / Groop, Leif / Mäkitie, Antti / Koskinen, Seppo / Salomaa, Veikko / Palotie, Aarno / Ripatti, Samuli / Palotie, Tuula

BMJ open

2018 Volume 8, Issue 10, Page(s) e022752

Abstract: Objective: To evaluate if obstructive sleep apnoea (OSA) modifies the risk of coronary heart disease, type 2 diabetes (T2D) and diabetic complications in a gender-specific fashion.: Design and setting: A longitudinal population-based study with up to ...

Abstract	Objective: To evaluate if obstructive sleep apnoea (OSA) modifies the risk of coronary heart disease, type 2 diabetes (T2D) and diabetic complications in a gender-specific fashion. Design and setting: A longitudinal population-based study with up to 25-year follow-up data on 36 963 individuals (>500 000 person years) from three population-based cohorts: the FINRISK study, the Health 2000 Cohort Study and the Botnia Study. Main outcome measures: Incident coronary heart disease, diabetic kidney disease, T2D and all-cause mortality from the Finnish National Hospital Discharge Register and the Finnish National Causes-of-Death Register. Results: After adjustments for age, sex, region, high-density lipoprotein (HDL) and total cholesterol, current cigarette smoking, body mass index, hypertension, T2D baseline and family history of stroke or myocardial infarction, OSA increased the risk for coronary heart disease (HR=1.36, p=0.0014, 95% CI 1.12 to 1.64), particularly in women (HR=2.01, 95% CI 1.31 to 3.07, p=0.0012). T2D clustered with OSA independently of obesity (HR=1.48, 95% CI 1.26 to 1.73, p=9.11×[Formula: see text]). The risk of diabetic kidney disease increased 1.75-fold in patients with OSA (95% CI 1.13 to 2.71, p=0.013). OSA increased the risk for coronary heart disease similarly among patients with T2D and in general population (HR=1.36). All-cause mortality was increased by OSA in diabetic individuals (HR=1.35, 95% CI 1.06 to 1.71, p=0.016). Conclusion: OSA is an independent risk factor for coronary heart disease, T2D and diabetic kidney disease. This effect is more pronounced even in women, who until now have received less attention in diagnosis and treatment of OSA than men.
MeSH term(s)	Adult ; Aged ; Comorbidity ; Coronary Disease/blood ; Coronary Disease/etiology ; Coronary Disease/mortality ; Coronary Disease/physiopathology ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/etiology ; Diabetes Mellitus, Type 2/mortality ; Diabetes Mellitus, Type 2/physiopathology ; Female ; Finland/epidemiology ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Polysomnography ; Population Surveillance ; Predictive Value of Tests ; Prevalence ; Risk Assessment ; Risk Factors ; Sleep Apnea, Obstructive/blood ; Sleep Apnea, Obstructive/complications ; Sleep Apnea, Obstructive/mortality ; Sleep Apnea, Obstructive/physiopathology
Language	English
Publishing date	2018-10-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2747269-3
ISSN	2044-6055 ; 2044-6055 ; 2053-3624
ISSN (online)	2044-6055
ISSN	2044-6055 ; 2053-3624
DOI	10.1136/bmjopen-2018-022752
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