Genome-wide meta-analyses of non-response to antidepressants identify novel loci and potential drugs.

Antidepressants exhibit a considerable variation in efficacy, and increasing evidence suggests that individual genetics contribute to antidepressant treatment response. Here, we combined data on antidepressant non-response measured using rating scales for depressive symptoms, questionnaires of treatment effect, and data from electronic health records, to increase statistical power to detect genomic loci associated with non-response to antidepressants in a total sample of 135,471 individuals prescribed antidepressants (25,255 non-responders and 110,216 responders). We performed genome-wide association meta-analyses, genetic correlation analyses, leave-one-out polygenic prediction, and bioinformatics analyses for genetically informed drug prioritization.

Parkinson's Disease Polygenic Risk Score and Neurological Involvement in Carriers of the FMR1 Premutation Allele: A Case for Genetic Modifier.

Background: Premutation alleles of the FMR1 X-linked gene containing CGG repeat expansions ranging from 55 to 200 are associated with diverse late-onset neurological involvements, including most severe disorder termed Fragile X-associated Tremor/Ataxia Syndrome (FXTAS). It is intriguing that at least one-third of male, and a much lower than predicted from the X-linkage proportion of female carriers are free of this syndrome. This suggests the existence of secondary genetic factors modifying the risk of neurological involvements in these carriers.

The Association Between Bilingual Animal Naming and Memory Among Bilingual Mexican American Older Adults.

Background: Monolingual cognitive assessments are standard for bilinguals; the value of bilingual assessment is unknown. Since declines in animal naming accompany memory declines in dementia, we examined the association between bilingual animal naming and memory among bilingual Mexican American (MA) older adults.

Methods: Bilingual MA (n = 155) completed the Harmonized Cognitive Assessment Protocol (HCAP) in a Texas community study.

Uncovering genetic loci and biological pathways associated with age-related cataracts through GWAS meta-analysis.

Age-related cataracts is a highly prevalent eye disorder that results in the clouding of the crystalline lens and is one of the leading causes of visual impairment and blindness. The disease is influenced by multiple factors including genetics, prolonged exposure to ultraviolet radiation, and a history of diabetes. However, the extent to which each of these factors contributes to the development of cataracts remains unclear.

Integrating Diversity, Culture, and Equity into the Neuropsychological Evaluation.

Cognition is influenced by a host of factors, including the patient's medical, psychiatric, and developmental history; sociocultural and demographic factors; modifiable behavioral factors; and structural and social determinants of health. Neuropsychological approaches include interpreting test data in the context of these factors to classify impairment and derive a cognitive diagnosis accurately. Failure to integrate an individual's sociodemographic, sociocultural, and developmental background can result in diagnostic errors, which have critical clinical implications for patient care.

Building national patient registries in Mexico: insights from the MexOMICS Consortium.

Objective: To introduce MexOMICS, a Mexican Consortium focused on establishing electronic databases to collect, cross-reference, and share health-related and omics data on the Mexican population.

Methods: Since 2019, the MexOMICS Consortium has established three electronic-based registries: the Mexican Twin Registry (TwinsMX), Mexican Lupus Registry (LupusRGMX), and the Mexican Parkinson's Research Network (MEX-PD), designed and implemented using the Research Electronic Data Capture web-based application. Participants were enrolled through voluntary participation and on-site engagement with medical specialists.

TwinsMX: Exploring the Genetic and Environmental Influences on Health Traits in the Mexican Population.

TwinsMX registry is a national research initiative in Mexico that aims to understand the complex interplay between genetics and environment in shaping physical and mental health traits among the country's population. With a multidisciplinary approach, TwinsMX aims to advance our knowledge of the genetic and environmental mechanisms underlying ethnic variations in complex traits and diseases, including behavioral, psychometric, anthropometric, metabolic, cardiovascular and mental disorders. With information gathered from over 2800 twins, this article updates the prevalence of several complex traits; and describes the advances and novel ideas we have implemented such as magnetic resonance imaging.

Psychometric evaluation and linking of the PHQ-9, QIDS-C, and VQIDS-C in a real-world population with major depressive disorder.

Purpose: Major depressive disorder (MDD) is a leading cause of disability worldwide. An accurate assessment of depressive symptomology is crucial for clinical management and research. This study assessed the convergent validity, reliability, and total scale score interconversion across the 9-item Patient Health Questionnaire (PHQ-9) self-report, the 16-item Quick Inventory of Depressive Symptomatology-clinician report (QIDS-C) (two widely used clinical ratings) and the 5-item Very Brief Quick Inventory of Depressive Symptoms-clinician report (VQIDS-C), which evaluate the core features of MDD.

Investigating the Shared Genetic Etiology Between Parkinson's Disease and Depression.

Background: Depression is a common symptom in Parkinson's disease (PD), resulting from underlying neuropathological processes and psychological factors. However, the extent to which shared genetic risk factors contribute to the relationship between depression and PD is poorly understood.

Objective: To examine the effects of common genetic variants influencing the etiology of PD and depression risk at the genome-wide and local genomic regional level.

Associations of externalizing polygenic scores with externalizing disorders among Mexican youth.

Several studies have examined the association of externalizing polygenic scores (PGS) with externalizing symptoms in samples of European ancestry. However, less is known about the associations of externalizing polygenic vulnerability in relation to phenotypic externalizing disorders among individuals of different ancestries, such as Mexican youth. Here, we leveraged the largest genome-wide association study on externalizing behaviors that included over 1 million individuals of European ancestry to examine associations of externalizing PGS with a range of externalizing disorders in Mexican adolescents, and investigated whether adversity exposure in childhood moderated these associations.

Fructose intake from sugar-sweetened beverages is associated with a greater risk of hyperandrogenism in women: UK Biobank cohort study.

Objective: To assess the association between fructose consumption and serum sex hormone-binding globulin (SHBG), (free) testosterone, and risk of hyperandrogenism in a population-based cohort.

Design: An observational and genetic association study in participants of the UK Biobank (n = 136 384 and n = 383 392, respectively).

Methods: We assessed the relationship of (1) the intake of different sources of fructose (ie, total, fruit, fruit juice, and sugar-sweetened beverages [SSBs]) and (2) rs2304681 (a missense variant in the gene encoding ketohexokinase, used as an instrument of impaired fructose metabolism), with SHBG, total and free testosterone levels, and risk of hyperandrogenism (free androgen index >4.

Cross-national comparisons of later-life cognitive function using data from the Harmonized Cognitive Assessment Protocol (HCAP): Considerations and recommended best practices.

The Harmonized Cognitive Assessment Protocol (HCAP) is a major innovation that provides, for the first time, harmonized data for cross-national comparisons of later-life cognitive functions that are sensitive to linguistic, cultural, and educational differences across countries. However, cognitive function does not lend itself to direct comparison across diverse populations without careful consideration of the best practices for such comparisons. This perspective discusses theoretical and methodological considerations and offers a set of recommended best practices for conducting cross-national comparisons of risk factor associations using HCAP data.

Association between urinary lithiasis, other than struvite by crystallography and non-ureolytic bacteria.

The relationship between urinary tract infection caused by urease-producing bacteria and lithiasis due to struvite stones is well established in the literature. However, there is limited knowledge on whether non-urease producing bacteria can also promote crystallization. In our study, we analyzed the association between urinary lithiasis, other than struvite by crystallography and non-ureolytic bacteria, in 153 patients who underwent surgery for urinary stone.

Discontinuation of antidepressant treatment: a retrospective cohort study on more than 20,000 participants.

Background: Factors influencing antidepressant treatment discontinuation are poorly understood. In the present study, we aimed to estimate the prevalence of antidepressant treatment discontinuation and identify demographic characteristics, psychiatric comorbidities, and specific side effects associated with treatment discontinuation.

Methods: We leveraged data from the Australian Genetics of Depression Study (AGDS; N = 20,941) to perform a retrospective cohort study on antidepressant treatment discontinuation.

WITHDRAWN: Genome-wide risk prediction of primary open-angle glaucoma across multiple ancestries.

This manuscript has been withdrawn by medRxiv following a formal request by the QIMR Berghofer Medical Research Institute Research Integrity Office owing to lack of author consent.

Estimating the Genetic Contribution to Astigmatism and Myopia in the Mexican Population.

Astigmatism and myopia are two common ocular refractive errors that can impact daily life, including learning and productivity. Current knowledge suggests that the etiology of these conditions is the result of a complex interplay between genetic and environmental factors. Studies in populations of European ancestry have demonstrated a higher concordance of refractive errors in monozygotic (MZ) twins compared to dizygotic (DZ) twins.