Genetics of psycho-emotional well-being: genome-wide association study and polygenic risk score analysis

BackgroundPsycho-emotional well-being is essential for living a life of satisfaction and fulfillment. However, depression and anxiety have become the leading mental health issues worldwide, according to the World Health Organization. Both disorders have been linked to stress and other psychological factors. Their genetic basis remains understudied.MethodsIn 2020–2021, the psycho-emotional well-being of 30,063 Russians with no known psychiatric history was assessed using the Hospital Anxiety and Depression Scale (HADS) for general mental health and the HADS subscale A (anxiety) for anxiety. Following the original instructions, an anxiety score of ≥11 points was used as the anxiety threshold. A genome-wide association study was performed to find associations between anxiety and HADS/HADS-A scores using linear and logistic regressions based on HADS/HADS-A scores as binary and continuous variables, respectively. In addition, the links between anxiety, sociodemographic factors (such as age, sex, and employment), lifestyle (such as physical activity, sleep duration, and smoking), and markers of caffeine and alcohol metabolism were analyzed. To assess the risk of anxiety, polygenic risk score modeling was carried out using open-access software and principal component analysis (PCA) to simplify the calculations (ROC AUC = 89.4 ± 2.2% on the test set).ResultsThere was a strong positive association between HADS/HADS-A scores and sociodemographic factors and lifestyle. New single-nucleotide polymorphisms (SNPs) with genome-wide significance were discovered, which had not been associated with anxiety or other stress-related conditions but were located in genes previously associated with bipolar disorder, schizophrenia, or emotional instability. The CACNA1C variant rs1205787230 was associated with clinical anxiety (a HADS-A score of ≥11 points). There was an association between anxiety levels (HADS-A scores) and genes involved in the activity of excitatory neurotransmitters: PTPRN2 (rs3857647), DLGAP4 (rs8114927), and STK24 (rs9517326).ConclusionOur results suggest that calcium channels and monoamine neurotransmitters, as well as SNPs in genes directly or indirectly affecting neurogenesis and synaptic functions, may be involved in the development of increased anxiety. The role of some non-genetic factors and the clinical significance of physiological markers such as lifestyle were also demonstrated

Biological Age Predictors: The Status Quo and Future Trends

There is no single universal biomarker yet to estimate overall health status and longevity prospects. Moreover, a consensual approach to the very concept of aging and the means of its assessment are yet to be developed. Markers of aging could facilitate effective health control, more accurate life expectancy estimates, and improved health and quality of life. Clinicians routinely use several indicators that could be biomarkers of aging. Duly validated in a large cohort, models based on a combination of these markers could provide a highly accurate assessment of biological age and the pace of aging. Biological aging is a complex characteristic of chronological age (usually), health-to-age concordance, and medically estimated life expectancy. This study is a review of the most promising techniques that could soon be used in routine clinical practice. Two main selection criteria were applied: a sufficient sample size and reliability based on validation. The selected biological age calculators were grouped according to the type of biomarker used: (1) standard clinical and laboratory markers; (2) molecular markers; and (3) epigenetic markers. The most accurate were the calculators, which factored in a variety of biomarkers. Despite their demonstrated effectiveness, most of them require further improvement and cannot yet be considered for use in standard clinical practice. To illustrate their clinical application, we reviewed their use during the COVID-19 pandemic

Сидеропенічний синдром у студентської молоді

Латентный дефицит железа всегда предшествует железодефицитной анемии. Целью исследования было изучить частоту встречаемости клинических признаков латентного дефицита железа у молодежи. Обследовано 280 человек возрасте от 17 до 21 года. Использован анкетный метод с серией вопросов для выявления признаков сидеропенического и анемического синдромов, а также вопросов для выявления причин дефицита железа. Статистическая обработка проведена с использованием прикладной программы Microsoft office Excel 2013. Среди клинических признаков сидеропенического синдрома у студенческой молодежи отмечено преобладание извращения вкуса (16,79%) и обоняния (33,21%), мышечная слабость, боль в икроножных мышцах (29,64%), изменение со стороны ногтей и волос (46,79%), причем преобладание комплекса данных симптомов было отмечено у лиц женского пола. У 33,75% обследованных встречалась полименорея, причем их них 37,2% составили лица с сидеропеническим синдромом. У лиц, с количеством жалоб со стороны желудочно-кишечного тракта (две и более), наблюдается резкое увеличение частоты проявления сидеропенического синдрома (на 26,8%) по сравнению с респондентами, у которых жалобы отсутствуют.Латентний дефіцит заліза завжди передує залізодефіцитної анемії. Метою дослідження було вивчити частоту зустрічаємості клінічних ознак латентного дефіциту заліза у молоді. Обстежено 280 осіб віком від 17 до 21 року. Використаний анкетний метод з серією питань для виявлення ознак сидеропенічного і анемічного синдромів, а також питань для виявлення причин дефіциту заліза. Статистична обробка проведена з використанням прикладної програми Microsoft Office Excel 2013. Серед клінічних ознак сидеропенічного синдрому у студентської молоді спостерігалося переважання збочення смаку (16,79%) та нюху (33,21%), м’язова слабкість, біль у литкових м’язах (29, 64%), зміна з боку нігтів і волосся (46,79%), причому комплекс даних симптомів було відмічено переважно в осіб жіночої статі. У 33,75% обстежених зустрічалася поліменорея, причому з них 37,2% склали особи з сидеропенічним синдромом. У осіб з кількістю скарг з боку шлунково-кишкового тракту (дві і більше) спостерігається різке збільшення частоти проявів сидеропенічного синдрому (на 26,8%) у порівнянні з респондентами, у яких скарги відсутні.The latent iron deficit is always preceded to iron-deficient anaemia. A research aim was to study occurrence rate of clinical signs of latent iron deficit in adolescents. 280 individuals aged from 17 to 21 were involved into study. A questionnaire method with a series of questions was used to identify signs of sideropenic and anaemic syndromes, as well as questions to identify the causes of iron deficiency. Statistical processing was carried out by applying the Microsoft office Excel 2013. Among the clinical signs of syderopenic syndrome in the students we observed the predominance of olfactory perversion (33,21%), muscular weakness, pain gastrocnemius muscles (29,64%), taste perversion (16,79%), changes in the state of hair and nails (46,79%). This was mainly typical for female individuals. 33,75% of women had polymenorea, and 37,2% out of the were diagnosed to have a syderopenic syndrome. The individuals complaining on gastrointestinal problems (two or more) demonstrated a sharp increase in the frequency syderopenic syndrome occurance (by 26,8%) as compared to the respondents without the complaint

Data_Sheet_2_Genetics of psycho-emotional well-being: genome-wide association study and polygenic risk score analysis.docx

BackgroundPsycho-emotional well-being is essential for living a life of satisfaction and fulfillment. However, depression and anxiety have become the leading mental health issues worldwide, according to the World Health Organization. Both disorders have been linked to stress and other psychological factors. Their genetic basis remains understudied.MethodsIn 2020–2021, the psycho-emotional well-being of 30,063 Russians with no known psychiatric history was assessed using the Hospital Anxiety and Depression Scale (HADS) for general mental health and the HADS subscale A (anxiety) for anxiety. Following the original instructions, an anxiety score of ≥11 points was used as the anxiety threshold. A genome-wide association study was performed to find associations between anxiety and HADS/HADS-A scores using linear and logistic regressions based on HADS/HADS-A scores as binary and continuous variables, respectively. In addition, the links between anxiety, sociodemographic factors (such as age, sex, and employment), lifestyle (such as physical activity, sleep duration, and smoking), and markers of caffeine and alcohol metabolism were analyzed. To assess the risk of anxiety, polygenic risk score modeling was carried out using open-access software and principal component analysis (PCA) to simplify the calculations (ROC AUC = 89.4 ± 2.2% on the test set).ResultsThere was a strong positive association between HADS/HADS-A scores and sociodemographic factors and lifestyle. New single-nucleotide polymorphisms (SNPs) with genome-wide significance were discovered, which had not been associated with anxiety or other stress-related conditions but were located in genes previously associated with bipolar disorder, schizophrenia, or emotional instability. The CACNA1C variant rs1205787230 was associated with clinical anxiety (a HADS-A score of ≥11 points). There was an association between anxiety levels (HADS-A scores) and genes involved in the activity of excitatory neurotransmitters: PTPRN2 (rs3857647), DLGAP4 (rs8114927), and STK24 (rs9517326).ConclusionOur results suggest that calcium channels and monoamine neurotransmitters, as well as SNPs in genes directly or indirectly affecting neurogenesis and synaptic functions, may be involved in the development of increased anxiety. The role of some non-genetic factors and the clinical significance of physiological markers such as lifestyle were also demonstrated.</p

Data_Sheet_1_Genetics of psycho-emotional well-being: genome-wide association study and polygenic risk score analysis.docx

BackgroundPsycho-emotional well-being is essential for living a life of satisfaction and fulfillment. However, depression and anxiety have become the leading mental health issues worldwide, according to the World Health Organization. Both disorders have been linked to stress and other psychological factors. Their genetic basis remains understudied.MethodsIn 2020–2021, the psycho-emotional well-being of 30,063 Russians with no known psychiatric history was assessed using the Hospital Anxiety and Depression Scale (HADS) for general mental health and the HADS subscale A (anxiety) for anxiety. Following the original instructions, an anxiety score of ≥11 points was used as the anxiety threshold. A genome-wide association study was performed to find associations between anxiety and HADS/HADS-A scores using linear and logistic regressions based on HADS/HADS-A scores as binary and continuous variables, respectively. In addition, the links between anxiety, sociodemographic factors (such as age, sex, and employment), lifestyle (such as physical activity, sleep duration, and smoking), and markers of caffeine and alcohol metabolism were analyzed. To assess the risk of anxiety, polygenic risk score modeling was carried out using open-access software and principal component analysis (PCA) to simplify the calculations (ROC AUC = 89.4 ± 2.2% on the test set).ResultsThere was a strong positive association between HADS/HADS-A scores and sociodemographic factors and lifestyle. New single-nucleotide polymorphisms (SNPs) with genome-wide significance were discovered, which had not been associated with anxiety or other stress-related conditions but were located in genes previously associated with bipolar disorder, schizophrenia, or emotional instability. The CACNA1C variant rs1205787230 was associated with clinical anxiety (a HADS-A score of ≥11 points). There was an association between anxiety levels (HADS-A scores) and genes involved in the activity of excitatory neurotransmitters: PTPRN2 (rs3857647), DLGAP4 (rs8114927), and STK24 (rs9517326).ConclusionOur results suggest that calcium channels and monoamine neurotransmitters, as well as SNPs in genes directly or indirectly affecting neurogenesis and synaptic functions, may be involved in the development of increased anxiety. The role of some non-genetic factors and the clinical significance of physiological markers such as lifestyle were also demonstrated.</p