Genetic diversity and signatures of selection in Icelandic horses and Exmoor ponies.

BACKGROUND: The Icelandic horse and Exmoor pony are ancient, native breeds, adapted to harsh environmental conditions and they have both undergone severe historic bottlenecks. However, in modern days, the selection pressures on these breeds differ substantially. The aim of this study was to assess genetic diversity in both breeds through expected (HE) and observed heterozygosity (HO) and effective population size (Ne). Furthermore, we aimed to identify runs of homozygosity (ROH) to estimate and compare genomic inbreeding and signatures of selection in the breeds. RESULTS: HO was estimated at 0.34 and 0.33 in the Icelandic horse and Exmoor pony, respectively, aligning closely with HE of 0.34 for both breeds. Based on genomic data, the Ne for the last generation was calculated to be 125 individuals for Icelandic horses and 42 for Exmoor ponies. Genomic inbreeding coefficient (FROH) ranged from 0.08 to 0.20 for the Icelandic horse and 0.12 to 0.27 for the Exmoor pony, with the majority of inbreeding attributed to short ROHs in both breeds. Several ROH islands associated with performance were identified in the Icelandic horse, featuring target genes such as DMRT3, DOCK8, EDNRB, SLAIN1, and NEURL1. Shared ROH islands between both breeds were linked to metabolic processes (FOXO1), body size, and the immune system (CYRIB), while private ROH islands in Exmoor ponies were associated with coat colours (ASIP, TBX3, OCA2), immune system (LYG1, LYG2), and fertility (TEX14, SPO11, ADAM20). CONCLUSIONS: Evaluations of genetic diversity and inbreeding reveal insights into the evolutionary trajectories of both breeds, highlighting the consequences of population bottlenecks. While the genetic diversity in the Icelandic horse is acceptable, a critically low genetic diversity was estimated for the Exmoor pony, which requires further validation. Identified signatures of selection highlight the differences in the use of the two breeds as well as their adaptive trait similarities. The results provide insight into genomic regions under selection pressure in a gaited performance horse breed and various adaptive traits in small-sized native horse breeds. This understanding contributes to preserving genetic diversity and population health in these equine populations.

Start codon variant in LAG3 is associated with decreased LAG-3 expression and increased risk of autoimmune thyroid disease.

Autoimmune thyroid disease (AITD) is a common autoimmune disease. In a GWAS meta-analysis of 110,945 cases and 1,084,290 controls, 290 sequence variants at 225 loci are associated with AITD. Of these variants, 115 are previously unreported. Multiomics analysis yields 235 candidate genes outside the MHC-region and the findings highlight the importance of genes involved in T-cell regulation. A rare 5'-UTR variant (rs781745126-T, MAF = 0.13% in Iceland) in LAG3 has the largest effect (OR = 3.42, P = 2.2 × 10-16) and generates a novel start codon for an open reading frame upstream of the canonical protein translation initiation site. rs781745126-T reduces mRNA and surface expression of the inhibitory immune checkpoint LAG-3 co-receptor on activated lymphocyte subsets and halves LAG-3 levels in plasma among heterozygotes. All three homozygous carriers of rs781745126-T have AITD, of whom one also has two other T-cell mediated diseases, that is vitiligo and type 1 diabetes. rs781745126-T associates nominally with vitiligo (OR = 5.1, P = 6.5 × 10-3) but not with type 1 diabetes. Thus, the effect of rs781745126-T is akin to drugs that inhibit LAG-3, which unleash immune responses and can have thyroid dysfunction and vitiligo as adverse events. This illustrates how a multiomics approach can reveal potential drug targets and safety concerns.

Trends in gestational diabetes in Iceland before and after guideline changes in 2012: a nationwide study from 1997 to 2020.

Internationally accepted diagnostic criteria recommendations for gestational diabetes (GDM) in 2010 resulted in a rise in global prevalence of GDM. Our aim was to describe the trends in GDM before and after Icelandic guideline changes in 2012 and the trends in pregestational diabetes (PGDM). The study included all singleton births (N = 101 093) in Iceland during 1997-2020. Modified Poisson regression models were used to estimate prevalence ratios (PRs) with 95% confidence intervals (CIs) for risk of GDM overall and by maternal age group, as well as overall risk of PGDM, according to time period of birth. The overall prevalence of GDM by time period of birth ranged from 0.6% (N = 101) in 1997-2000 to 16.2% (N = 2720) in 2017-2020, and the prevalence of PGDM ranged from 0.4% (N = 57) in 1997-2000 to 0.7% (N = 120) in 2017-2020. The overall relative GDM prevalence rate difference before and after 2012 was 380%, and the largest difference was found among women aged <25 years at 473%. Risk of GDM increased in 2017-2020 (PR 14.21, CI 11.45, 17.64) compared to 1997-2000 and was highest among women aged >34 years with PR 19.46 (CI 12.36, 30.63) in 2017-2020. Prevalence rates of GDM and PGDM increased during the study period. An accelerated rate of increase in GDM was found after 2012, overall, and among all maternal age groups. Women aged >34 years had the greatest risk of GDM throughout all time periods, while women aged <25 years appear to have a higher relative rate difference after 2012.

Classifying national drinking patterns in Europe between 2000 and 2019: A clustering approach using comparable exposure data.

BACKGROUND AND AIMS: Previously identified national drinking patterns in Europe lack comparability and might be no longer be valid due to changes in economic conditions and policy frameworks. We aimed to identify the most recent alcohol drinking patterns in Europe based on comparable alcohol exposure indicators using a data-driven approach, as well as identifying temporal changes and establishing empirical links between these patterns and indicators of alcohol-related harm. DESIGN: Data from the World Health Organization's monitoring system on alcohol exposure indicators were used. Repeated cross-sectional hierarchical cluster analyses were applied. Differences in alcohol-attributable harm between clusters of countries were analyzed via linear regression. SETTING: European Union countries, plus Iceland, Norway and Ukraine, for 2000, 2010, 2015 and 2019. PARTICIPANTS/CASES: Observations consisted of annual country data, at four different time points for alcohol exposure. Harm indicators were only included for 2019. MEASUREMENTS: Alcohol exposure indicators included alcohol per capita consumption (APC), beverage-specific consumption and prevalence of drinking status indicators (lifetime abstainers, current drinkers, former drinkers and heavy episodic drinking). Alcohol-attributable harm was measured using age-standardized alcohol-attributable Disability-Adjusted Life Years (DALYs) lost and deaths per 100 000 people. FINDINGS: The same six clusters were identified in 2019, 2015 and 2010, mainly characterized by type of alcoholic beverage and prevalence drinking status indicators, with geographical interpretation. Two-thirds of the countries remained in the same cluster over time, with one additional cluster identified in 2000, characterized by low APC. The most recent drinking patterns were shown to be significantly associated with alcohol-attributable deaths and DALY rates. Compared with wine-drinking countries, the mortality rate per 100 000 people was significantly higher in Eastern Europe with high spirits and 'other' beverage consumption [ ß ^ = 90, 95% confidence interval (CI) = 55-126], and in Eastern Europe with high lifetime abstainers and high spirits consumption ( ß ^ = 42, 95% CI = 4-78). CONCLUSIONS: European drinking patterns appear to be clustered by level of beverage-specific consumption, with heavy episodic drinkers, current drinkers and lifetime abstainers being distinguishing factors between clusters. Despite the overall stability of the clusters over time, some countries shifted between drinking patterns from 2000 to 2019. Overall, patterns of drinking in the European Union seem to be stable and partly determined by geographical proximity.

The rate and nature of mitochondrial DNA mutations in human pedigrees.

We examined the rate and nature of mitochondrial DNA (mtDNA) mutations in humans using sequence data from 64,806 contemporary Icelanders from 2,548 matrilines. Based on 116,663 mother-child transmissions, 8,199 mutations were detected, providing robust rate estimates by nucleotide type, functional impact, position, and different alleles at the same position. We thoroughly document the true extent of hypermutability in mtDNA, mainly affecting the control region but also some coding-region variants. The results reveal the impact of negative selection on viable deleterious mutations, including rapidly mutating disease-associated 3243A>G and 1555A>G and pre-natal selection that most likely occurs during the development of oocytes. Finally, we show that the fate of new mutations is determined by a drastic germline bottleneck, amounting to an average of 3 mtDNA units effectively transmitted from mother to child.

Green-house gas fluxes and soil microbial functional genes abundance in saturated and drained peatlands in South-West Iceland.

The drainage of peatlands followed by land use conversion significantly impacts on the fluxes of green-house gases (GHGs, i.e. CO2, CH4, and N2O) to and from the atmosphere, driven by changes in soil properties and microbial communities. In this study, we compared saturated peatlands with drained ones used for sheep grazing or cultivated, which are common in South-West Iceland. These areas exhibit different degrees of soil saturation and nitrogen (N) content, reflecting the anthropic pressure gradient. We aimed at covering knowledge gaps about lack of estimates on N2O fluxes and drainage, by assessing the emissions of GHGs, and the impact of land conversion on these emissions. Moreover, we investigated soil microbial community functional diversity, and its connection with processes contributing to GHGs emission. GHGs emissions differed between saturated and drained peatlands, with increased soil respiration rates (CO2 emissions) and N mineralization (N2O), consistent with the trend of anthropogenic pressure. Drainage drastically reduced methane (CH4) emissions but increased CO2 emissions, resulting in a higher global warming potential (GWP). Cultivation, involving occasional tillage and fertilization, further increased N2O emissions, mediated by higher N availability and conditions favorable to nitrification. Functional genes mirrored the overall trend, showing a shift from prevalent methanogenic archaea (mcrA) in saturated peatlands to nitrifiers (amoA) in drained-cultivated areas. Environmental variables and nutrient content were critical factors affecting community composition in both environments, which overall affected the GHGs emissions and the relative contribution of the three gases.

Nurses' attitudes to family importance in nursing care: A two-sited cross-sectional study.

AIM: This study aimed to describe nurses' attitudes and beliefs towards the importance of family in nursing care and explore differences in nurses' attitudes and beliefs towards family-centered care between different healthcare institutions, such as community healthcare centers and hospitals. BACKGROUND: Family significantly affects the well-being and health of individuals. Therefore, nurses should support family engagement in nursing care. In recent years, family nursing research has emphasized the importance of teaching family nursing skills in continued education in healthcare institutions. Research has indicated that nurses who believe that illness concerns the family as a whole are more likely to involve the family in patient care. DESIGN: A cross-sectional research design was used. METHOD: Data were collected at one timepoint between March and September 2019 from 425 nurses working at the Primary Health Care Centers of the Capital Area (n=112) and in clinical settings at the University Hospital in Iceland (n=313). RESULTS: The main findings indicated that nurses working in the women-and-child division at the University Hospital reported significantly more positive attitudes towards family evolvement in patient care than nurses working in the intensive care or surgical units. For nurses working at healthcare centers, a significant difference was also found in the nurses' attitudes towards involving families in patient care. The nurses who were working in home care had significantly more positive attitudes when compared to those working in the infant and young children health promotion units. CONCLUSIONS: Greater collaboration is required between healthcare providers and families to improve the quality of care and health-related outcomes. Therefore, it is crucial to enhance nurses' knowledge about the importance of families during patient care. TWEETABLE ABSTRACT: This study aimed to describe nurses' attitudes and beliefs towards family care. Differences were found between nurse's attitudes by units but not by institutions.

[Prediction of cancer incidence and prevalence in Iceland up to the year 2040 - Icelandic Cancer Registry and Research Center].

INTRODUCTION: A large increase in new cancer cases is predicted worldwide, due to population growth, ageing and increased cancer risk. The age distribution of the Icelandic population is different from the other Nordic countries. The purpose of this study was to predict the number of new cancer cases in Iceland and other Nordic countries, and cancer survivors in Iceland, up to the year 2040. MATERIALS AND METHODS: Information on cancer diagnoses was retrieved from The Icelandic Cancer Registry and information on population projections from Statistics Iceland. Well known methods for population projection were used to predict the number of new cancer cases in 2040, but adjusted to consider Icelandic circumstances. It is also based on more recent data than is accessible elsewhere. Three different methods were used to estimate the number of survivors in 2040 and are presented here for the first time. RESULTS: In 2040 the predicted yearly average number of new cancer cases in Iceland will be up to 2,903 [95% CI 2.841-2.956], a 57% increase compared with 2022. The increase is higher in Iceland than in other Nordic countries (Norway 41%, Sweden 24%, Denmark 23%, Finland 21%). In 2022, the number of cancer survivors was around 17,500 and is predicted to be between 24,500 and 31,000 in 2040. CONCLUSION: The main reason for the predicted increase of cancer cases and survivors is population trends, especially the ageing of the population. This expected increase in the number of cancer patients and improved survival will increase the demand for healthcare.

Advanced Monitoring of H2S Injection through the Coupling of Reactive Transport Models and Geophysical Responses.

Hydrogen sulfide (H2S), an environmentally harmful pollutant, is a byproduct of geothermal energy production. To reduce the H2S emissions, H2S-charged water is injected into the basaltic subsurface, where it mineralizes to iron sulfides. Here, we couple geophysical induced polarization (IP) measurements in H2S injection wells and geochemical reactive transport models (RTM) to monitor the H2S storage efforts in the subsurface of Nesjavellir, one of Iceland's most productive geothermal fields. An increase in the IP response after 40 days of injection indicates iron-sulfide formation near the injection well. Likewise, the RTM shows that iron sulfides readily form at circumneutral to alkaline pH conditions, and the iron supply from basalt dissolution limits its formation. Agreement in the trends of the magnitude and distribution of iron-sulfide formation between IP and RTM suggests that coupling the methods can improve the monitoring of H2S mineralization by providing insight into the parameters influencing iron-sulfide formation. In particular, accurate fluid flow parameters in RTMs are critical to validate the predictions of the spatial distribution of subsurface iron-sulfide formation over time obtained through IP observations. This work establishes a foundation for expanding H2S sequestration monitoring efforts and a framework for coupling geophysical and geochemical site evaluations in environmental studies.

Iceland: an underestimated hub for the spread of high-pathogenicity avian influenza viruses in the North Atlantic.

High-pathogenicity avian influenza viruses (HPAIVs) of the goose/Guangdong lineage are enzootically circulating in wild bird populations worldwide. This increases the risk of entry into poultry production and spill-over to mammalian species, including humans. Better understanding of the ecological and epizootiological networks of these viruses is essential to optimize mitigation measures. Based on full genome sequences of 26 HPAIV samples from Iceland, which were collected between spring and autumn 2022, as well as 1 sample from the 2023 summer period, we show that 3 different genotypes of HPAIV H5N1 clade 2.3.4.4b were circulating within the wild bird population in Iceland in 2022. Furthermore, in 2023 we observed a novel introduction of HPAIV H5N5 of the same clade to Iceland. The data support the role of Iceland as an utmost northwestern distribution area in Europe that might act also as a potential bridging point for intercontinental spread of HPAIV across the North Atlantic.

Association Between Autoimmune Diseases and Monoclonal Gammopathy of Undetermined Significance : An Analysis From a Population-Based Screening Study.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. In previous registry-based, retrospective studies, autoimmune diseases have been associated with MGUS. However, these studies were not based on a screened population and are therefore prone to ascertainment bias. OBJECTIVE: To examine whether MGUS is associated with autoimmune diseases. DESIGN: A cross-sectional study within iStopMM (Iceland Screens, Treats, or Prevents MM), a prospective, population-based screening study of MGUS. SETTING: Icelandic population of adults aged 40 years or older. PATIENTS: 75 422 persons screened for MGUS. MEASUREMENTS: Poisson regression for prevalence ratios (PRs) of MGUS among persons with or without an autoimmune disease, adjusted for age and sex. RESULTS: A total of 10 818 participants had an autoimmune disorder, of whom 599 had MGUS (61 with a prior clinical diagnosis and 538 diagnosed at study screening or evaluation). A diagnosis of an autoimmune disease was not associated with MGUS (PR, 1.05 [95% CI, 0.97 to 1.15]). However, autoimmune disease diagnoses were associated with a prior clinical diagnosis of MGUS (PR, 2.11 [CI, 1.64 to 2.70]). LIMITATION: Registry data were used to gather information on autoimmune diseases, and the homogeneity of the Icelandic population may limit the generalizability of these results. CONCLUSION: The study did not find an association between autoimmune disease and MGUS in a systematically screened population. Previous studies not done in systematically screened populations have likely been subject to ascertainment bias. The findings indicate that recommendations to routinely screen patients with autoimmune disease for MGUS may not be warranted. PRIMARY FUNDING SOURCE: The International Myeloma Foundation and the European Research Council.

[Cancer registration in Iceland for 70 years - incidence, mortality and survival].

INTRODUCTION: The Icelandic Cancer Registry (ICR) was founded seventy years ago by the Icelandic Cancer Society. In 2007 the ICR became one of the health registers of the Directorate of Health. In this paper we present cancer incidence, mortality, and survival in Iceland over 70 years. MATERIAL AND METHODS: The ICR receives information on cancer diagnoses from histopathological laboratories, the Hospital Discharge Registry and the Cause of Death Registry. Iceland participates in the Nordic cancer database NORDCAN. Because of the small population size, random variation in numbers is very prominent. Therefore, data from ICR are published as five-year averages. RESULTS: For all malignancies combined, age-standardized incidence (ASI) in men rose steadily until around 15 years ago when a decline started. This is in line with prostate- and lung cancer incidence trends. In women, the ASI was lower than in men, but it is still on the rise despite declining lung cancer incidence. ASI for breast cancer, the most common cancer in women, is increasing. Simultaneously, cancer mortality for both sexes has declined in recent years and cancer survival is improving. CONCLUSIONS: Population-based cancer registration for over 70 years makes it possible to monitor the epidemiology of cancer in Iceland and compare with other countries. The changes in trends in ASI are in line with changes of cancer risk factors and diagnostic policy. The decline in cancer mortality and improvement in survival reflects advances in cancer treatment as well as effects of early detection and prevention.

The association between waterbirth and perineal injury or other adverse outcomes among low-risk women with physiological birth: Results from the Nordic Home Birth Cohort Study.

PROBLEM/BACKGROUND: Immersion in water has known benefits, such as reducing pain and shortening the duration of labour. The relationship between waterbirth and perineal injury remains unclear. AIM: To compare the incidence of perineal injury in waterbirth and birth on land among low-risk women. Secondary outcomes were postpartum haemorrhage and 5-minute Apgar scores <7. METHODS: Prospective cohort study of 2875 low-risk women who planned a home birth in Denmark, Iceland, Norway, and Sweden in 2008-2013 and had a spontaneous vaginal birth without intervention. Descriptive statistics and logistic regression were performed. FINDINGS: A total of 942 women had a waterbirth, and 1933 gave birth on land. The groups differed in their various background variables. Multiparous women had moderately lower rates of intact perineum (59.3% vs. 63.9%) and primiparous women had lower rates of episiotomies (1.1% vs. 4.8%) in waterbirth than in birth on land. No statistically significant differences were detected in adjusted regression analysis on intact perineum in waterbirth (primiparous women's aOR = 1.03, CI 0.68-1.58; multiparous women's aOR = 0.84, CI 0.67-1.05). The rates of sphincter injuries (0.9% vs. 0.6%) were low in both groups. No significant differences were detected in secondary outcomes. DISCUSSION: The decreased incidence of intact perineum among multiparous women was modest and inconclusive, and the prevalence of sphincter injury was low. CONCLUSION: Low-risk women contemplating waterbirth should be advised to weigh the risks and benefits detected in this study against previously established benefits of waterbirth and should make an informed choice based on their values.

Enantiomeric profile of amphetamines in seized drug samples and in blood of impaired drivers in Iceland: The rise of (R)-methamphetamine?

Amphetamine (AMP) and methamphetamine (METH) use is increasing globally. Illegal AMP is generally a racemic mixture, whereas AMP-containing attention-deficit hyperactivity disorder drugs prescribed in Iceland consist of S-AMP. AMP is also a main metabolite of interest after METH intake. Distinguishing between legal and illegal AMP intake is vital in forensic toxicology. A chiral UPLC-MS-MS method was used to determine the enantiomeric profile of AMP and METH in circulation in Iceland by analysing blood samples from drivers suspected of driving under the influence of drugs (DUID) and seized drug samples from 2021 and 2022. All seized AMP samples (n = 48) were racemic, whereas all but one seized METH sample (n = 26) were enantiopure. Surprisingly, a large portion of the enantiopure METH samples was R-METH. DUID blood samples positive for AMP (n = 564) had a median blood concentration of 180 ng/mL (range 20-2770 ng/mL) and a median enantiomeric fraction (EFR) of 0.54 (range 0-0.73), whereas samples positive for METH (n = 236) had a median blood concentration of 185 ng/mL (range 20-2300 ng/mL) and a median EFR of 0.23 (range 0-1). The findings of this study show a significantly lower blood concentration in drivers with only S-AMP detected compared with when the R-isomer is also detected. No significant difference in blood concentration was detected between the sample groups containing S-METH, R-METH or both enantiomers. The occurrence of R-METH in both seized drug samples and DUID cases indicates a change in drug supply and a need for better scientific knowledge on R-METH abuse.

Diversity in the internal functional feeding elements of sympatric morphs of Arctic charr (Salvelinus alpinus).

The diversity of functional feeding anatomy is particularly impressive in fishes and correlates with various interspecific ecological specializations. Intraspecific polymorphism can manifest in divergent feeding morphology and ecology, often along a benthic-pelagic axis. Arctic charr (Salvelinus alpinus) is a freshwater salmonid known for morphological variation and sympatric polymorphism and in Lake Þingvallavatn, Iceland, four morphs of charr coexist that differ in preferred prey, behaviour, habitat use, and external feeding morphology. We studied variation in six upper and lower jaw bones in adults of these four morphs using geometric morphometrics and univariate statistics. We tested for allometric differences in bone size and shape among morphs, morph effects on bone size and shape, and divergence along the benthic-pelagic axis. We also examined the degree of integration between bone pairs. We found differences in bone size between pelagic and benthic morphs for two bones (dentary and premaxilla). There was clear bone shape divergence along a benthic-pelagic axis in four bones (dentary, articular-angular, premaxilla and maxilla), as well as allometric shape differences between morphs in the dentary. Notably for the dentary, morph explained more shape variation than bone size. Comparatively, benthic morphs possess a compact and taller dentary, with shorter dentary palate, consistent with visible (but less prominent) differences in external morphology. As these morphs emerged in the last 10,000 years, these results indicate rapid functional evolution of specific feeding structures in arctic charr. This sets the stage for studies of the genetics and development of rapid and parallel craniofacial evolution.

[Perioperative stroke after aortic valve replacement for aortic stenosis - incidence, risk factors and short-term outcome].

INTRODUCTION: One of the most serious complications of surgical aortic valve replacement (SAVR) is stroke that can result in increased rates of complications, morbidity and mortality postoperatively. The aim of this study was to investigate incidence, risk factors and short-term outcome in a well defined cohort of SAVR-patients. MATERIALS AND METHOD: A retrospective study on 740 consecutive aortic stenosis patients who underwent SAVR in Iceland 2002-2019. Patients with stroke were compared with non-stroke patients; including preoperative risk factors of cardiovascular disease, echocardiogram-results, rate of early postoperative complications other than stroke and 30 day mortality. RESULTS: Mean age was 71 yrs (34% females) with 57% of the patients receiving stented bioprosthesis, 31% a stentless Freestyle®-valve and 12% a mechanical valve. Mean EuroSCORE-II was 3.6, with a maximum preop-gradient of 70 mmHg and an estimated valvular area of 0.73 cm2. Thirteen (1.8%) patients were diagnosed with stroke where hemiplegia (n=9), loss of consciousness (n=3) and/or aphasia (n=4) were the most common presenting symptoms. In 70% of cases the neurological symptoms resolved or disappeared in the first weeks and months after surgery. Only one patient out of 13 died within 30-days (7.7%). Stroke-patients had significantly lower BMI than non-stroke patients, but other risk factors of cardiovascular diseases, intraoperative factors or the rate of other severe postoperative complications than stroke were similar between groups. Total length of stay was 14 days vs. 10 days median, including 2 vs. 1 days in the ICU, in the stroke and non-stroke-groups, respectively. CONCLUSIONS: The rate of stroke after SAVR was low (1.8%) and in line with other similar studies. Although a severe complication, most patients with perioperative stroke survived 30 days postoperatively and in majority of cases neurological symptoms recovered.

Genetic association analysis of human median voice pitch identifies a common locus for tonal and non-tonal languages.

The genetic influence on human vocal pitch in tonal and non-tonal languages remains largely unknown. In tonal languages, such as Mandarin Chinese, pitch changes differentiate word meanings, whereas in non-tonal languages, such as Icelandic, pitch is used to convey intonation. We addressed this question by searching for genetic associations with interindividual variation in median pitch in a Chinese major depression case-control cohort and compared our results with a genome-wide association study from Iceland. The same genetic variant, rs11046212-T in an intron of the ABCC9 gene, was one of the most strongly associated loci with median pitch in both samples. Our meta-analysis revealed four genome-wide significant hits, including two novel associations. The discovery of genetic variants influencing vocal pitch across both tonal and non-tonal languages suggests the possibility of a common genetic contribution to the human vocal system shared in two distinct populations with languages that differ in tonality (Icelandic and Mandarin).