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1.
BMC Med Educ ; 21(1): 479, 2021 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-34493263

RESUMEN

BACKGROUND: Residents need to be trained across the boundaries of their own specialty to prepare them for collaborative practice. Intraprofessional learning (i.e. between individuals of different disciplines within the same profession) has received little attention in the postgraduate medical education literature, in contrast to the extensive literature on interprofessional learning between individuals of different professions. To address this gap, we performed a scoping review to investigate what and how residents learn from workplace-related intraprofessional activities, and what factors influence learning. METHODS: The PRISMA guidelines were used to conduct a scoping review of empirical studies on intraprofessional workplace learning in postgraduate medical education published between 1 January 2000 to 16 April 2020 in Pubmed, Embase, PsycINFO, ERIC and Web of Science. This study applied 'best fit' framework-based synthesis to map the existing evidence, using the presage-process-product (3P) model developed by Tynjälä (2013). RESULTS: Four thousand three hundred thirty records were screened, and 37 articles were included. This review identified influencing (presage) factors that derived from the sociocultural environment, learner and learning context. Studies described that complexity of care can both facilitate and hinder learning. Furthermore, intraprofessional learning is threatened by professional stereotyping and negative perceptions, and awareness of learning opportunities and explicit reflection are critical in intraprofessional workplace learning. Studies described a range of informal and formal intraprofessional activities (process) under the headings of collaboration in clinical practice, rotations or placements, formal educational sessions and simulated workplace training. In general, learners responded well and their attitudes and perceptions improved, learners reported increased knowledge and skills and positive behavioural changes (product). Learning outcomes were reported in the domains of patient-centred care, collaborative attitudes and respect, mutual knowledge and understanding, collaborative decision making, communication, leadership, teamwork and reflexivity. CONCLUSIONS: This review gives insight into the high learning potential of intraprofessional activities. Many of the included studies relied on self-reported perceptions of change, therefore, future research should focus on generating more robust evidence including objectively examined outcome measures. This review offers a comprehensive overview of the factors that influence intraprofessional workplace learning in postgraduate medical education. Finally, we provide recommendations for enhancing intraprofessional learning in clinical practice.


Asunto(s)
Educación Médica , Lugar de Trabajo , Competencia Clínica , Humanos , Liderazgo
2.
Perspect Med Educ ; 8(1): 1-8, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30656533

RESUMEN

INTRODUCTION: In postgraduate medical education, group decision-making has emerged as an essential tool to evaluate the clinical progress of residents. Clinical competency committees (CCCs) have been set up to ensure informed decision-making and provide feedback regarding performance of residents. Despite this important task, it remains unclear how CCCs actually function in practice and how their performance should be evaluated. METHODS: In the prototyping phase of a design-based approach, a CCC meeting was developed, using three theoretical design principles: (1) data from multiple assessment tools and multiple perspectives, (2) a shared mental model and (3) structured discussions. The meetings were held in a university children's hospital and evaluated using observations, interviews with CCC members and an open-ended questionnaire among residents. RESULTS: The structured discussions during the meetings provided a broad outline of resident performance, including identification of problematic and excellent residents. A shared mental model about the assessment criteria had developed over time. Residents were not always satisfied with the feedback they received after the meeting. Feedback that had been provided to a resident after the first CCC meeting was not addressed in the second meeting. DISCUSSION: The principles that were used to design the CCC meeting were feasible in practice. Structured discussions, based on data from multiple assessment tools and multiple perspectives, provided a broad outline of resident performance. Residency programs that wish to implement CCCs can build on our design principles and adjust the prototype to their particular context. When running a CCC, it is important to consider feedback that has been provided to a resident after the previous meeting and to evaluate whether it has improved the resident's performance.


Asunto(s)
Competencia Clínica/normas , Toma de Decisiones Clínicas , Miembro de Comité , Retroalimentación , Evaluación de Programas y Proyectos de Salud , Educación Basada en Competencias , Educación de Postgrado en Medicina , Docentes Médicos , Humanos , Internado y Residencia/normas , Pediatría , Encuestas y Cuestionarios
3.
Eur Geriatr Med ; 10(3): 517-522, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34652805

RESUMEN

CONTEXT: With the growing complexity in health care, clinical uncertainty increases, even more so in geriatrics. Intolerance of clinical uncertainty can result in stress, burnout and additional costs. This makes tolerance of clinical uncertainty a highly relevant skill to learn. This study investigated how residents cope with clinical uncertainty and explored options to improve their tolerance of it. METHODS: We interviewed nine residents from the geriatric department of a university medical center and analyzed the interviews conform template analysis using the 'integrative model of uncertainty tolerance'. RESULTS: All residents experienced clinical uncertainty regularly and emphasized it was a relevant topic. Residents described clinical uncertainty as both negative and positive, explaining it was difficult to deal with and could lead to stress, but it also kept them focused, challenged them and stimulated learning. While most of the reported topics fitted in the theoretical model, the model did not reflect the dynamics of clinical uncertainty and lacked its consequences outside the workplace. Residents mainly responded to clinical uncertainty by asking supervisors and peers to double-check their decisions concerning a patient. Residents indicated that they barely discussed their own emotions, cognitions or learning processes with peers or their supervisors. They would welcome the incorporation of clinical uncertainty as standard theme in patient supervision and educational meetings. CONCLUSION: Clinical uncertainty is not a problem of an insecure, failing resident, but an inherent part of caring for complex geriatric patients. Residents deserve to be trained in tolerance of clinical uncertainty to improve their well-being and care for geriatric patients.

4.
PLoS One ; 13(12): e0209312, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30566457

RESUMEN

BACKGROUND: Medical schools aim to contribute to a pool of doctors who are ready for a future practice that will be ever-changing requiring collaboration skills and lifelong learning. They adapt their curricula and selection procedures to fulfil this responsibility. This study aims to determine whether two different selection procedures in one medical school, both matching the key characteristics of the subsequent curricula (one traditional, knowledge-based, and one recently designed for self directed learning and focusing on practice), select students with different personality traits as a side-effect. This perspective was chosen as personality has been related to the CanMeds competencies, innovation capacities, medical school performance and medical professional success. METHODS: A total of 621 students admitted through the new or the traditional selection procedure were invited to complete a Big Five Inventory questionnaire at the start of their Bachelor's programme. Using ANCOVA, we compared Big Five traits of students admitted through the new selection procedure (n = 196) and the traditional selection procedure (n = 425). RESULTS: The group of students admitted through the procedure matching the newly designed curriculum had a lower mean score on neuroticism (p < .01) and higher mean scores on conscientiousness, extraversion, agreeableness and openness (p < .001) than the other group. CONCLUSIONS: The findings of the current study indicate that the medical school population is influenced in terms of personality traits as a side-effect of a changing selection procedure. We recommend studying this mechanism and its implications further and using it more consciously in selection procedure design.


Asunto(s)
Curriculum , Educación de Pregrado en Medicina/métodos , Personalidad , Facultades de Medicina , Estudiantes de Medicina/psicología , Adolescente , Estudios de Cohortes , Femenino , Humanos , Masculino , Países Bajos , Adulto Joven
5.
Adv Med Educ Pract ; 9: 345-355, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29785147

RESUMEN

INTRODUCTION: Research on selection for medical school does not explore selection as a learning experience, despite growing attention for the learning effects of assessment in general. Insight in the learning effects allows us to take advantage of selection as an inclusive part of medical students' learning process to become competent professionals. The aims of this study at Radboud University Medical Center, the Netherlands, were 1) to determine whether students have learning experiences in the selection process, and, if so, what experiences; and 2) to understand what students need in order to utilize the learning effects of the selection process at the start of the formal curriculum. MATERIALS AND METHODS: We used focus groups to interview 30 students admitted in 2016 about their learning experiences in the selection process. Thematic analysis was used to explore the outcomes of the interviews and to define relevant themes. RESULTS: In the selection process, students learned about the curriculum, themselves, their relation to others, and the profession they had been selected to enter, although this was not explicitly perceived as learning. Students needed a connection between selection and the curriculum as well as feedback to be able to really use their learning experiences for their further development. DISCUSSION: Medical school selection qualifies as a learning experience, and students as well as medical schools can take advantage of this. We recommend a careful design of the selection procedure, integrating relevant selection learning experiences into the formal curriculum, providing feedback and explicitly approaching the selection and the formal curriculum as interconnected contributors to students' development.

6.
Adv Health Sci Educ Theory Pract ; 23(1): 187-200, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28601913

RESUMEN

In medical school selection, non-cognitive performance in particular correlates with performance in clinical practice. It is arguable, therefore, that selection should focus on non-cognitive aspects despite the predictive value of prior cognitive performance for early medical school performance. The aim of this study at Radboud University Medical Center, the Netherlands, is to determine the effects of admitting students through an autonomous non-cognitive procedure on early medical school performance. We compared their performance to the performance of students selected through an autonomous cognitive selection procedure, enrolling in the Bachelor's curriculum simultaneously. 574 students (2013 and 2014 cohorts), admitted through non-cognitive selection (based on portfolio, CASPer and MMI, n = 135) or cognitive selection (curriculum sample selection, n = 439) were included in the study. We compared dropout rates, course credits and grades, using logistic and linear regression. The dropout rate was the highest in the non-cognitive selection group (p < 0.001). Students admitted through non-cognitive selection more often obtained the highest grade for the nursing attachment (p = 0.02) and had a higher mean grade for the practical clinical course in year 3 (p = .04). No differences in course grades were found. The results indicate that students perform best on the elements of the curriculum that are represented most strongly in the selection procedure they had participated in. We recommend the use of curriculum sample procedures, resembling the early medical school curriculum,-whether it has a more cognitive or a more non-cognitive focus-, to select the students who are likely to be successful in the subsequent curriculum.


Asunto(s)
Cognición , Evaluación Educacional/métodos , Evaluación Educacional/estadística & datos numéricos , Criterios de Admisión Escolar/estadística & datos numéricos , Facultades de Medicina/normas , Estudiantes de Medicina/psicología , Estudiantes de Medicina/estadística & datos numéricos , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Países Bajos , Adulto Joven
7.
Adv Health Sci Educ Theory Pract ; 22(1): 43-56, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27107882

RESUMEN

In the Netherlands, students are admitted to medical school through (1) selection, (2) direct access by high pre-university Grade Point Average (pu-GPA), (3) lottery after being rejected in the selection procedure, or (4) lottery. At Radboud University Medical Center, 2010 was the first year we selected applicants. We designed a procedure based on tasks mimicking the reality of early medical school. Applicants took an online course followed by an on-site exam, resembling courses and exams in early medical school. Based on the exam scores, applicants were selected or rejected. The aim of our study is to determine whether curriculum sample selection explains performance in medical school and is preferable compared to selection based on performance in secondary school. We gathered data on the performance of students of three consecutive cohorts (2010-2012, N = 954). We compared medical school performance (course credits and grade points) of selected students to the three groups admitted in other ways, especially lottery admissions. In regression analyses, we controlled for out of context cognitive performance by adjusting for pu-GPA. Selection-admitted students outperformed lottery-admitted students on most outcome measures, unadjusted as well as adjusted for pu-GPA (p ≤ 0.05). They had higher grade points than non-selected lottery students, both unadjusted and adjusted for pu-GPA (p ≤ 0.025). Adjusted for pu-GPA, selection-admitted students and high-pu-GPA students performed equally. We recommend this selection procedure as it adds to secondary school cognitive performance for the general population of students, is efficient for large numbers of applicants and not labour-intensive.


Asunto(s)
Curriculum , Criterios de Admisión Escolar , Facultades de Medicina/organización & administración , Adolescente , Evaluación Educacional , Escolaridad , Femenino , Humanos , Masculino , Países Bajos , Adulto Joven
8.
Adv Health Sci Educ Theory Pract ; 22(4): 985-1009, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27853908

RESUMEN

Within the unique and complex settings of university hospitals, it is difficult to implement policy initiatives aimed at developing careers in and improving the quality of academic medical teaching because of the competing domains of medical research and patient care. Factors that influence faculty in making use of teaching policy incentives have remained underexplored. Knowledge of these factors is needed to develop theory on the successful implementation of medical teaching policy in university hospitals. To explore factors that influence faculty in making use of teaching policy incentives and to develop a conceptual model for implementation of medical teaching policy in university hospitals. We used the grounded theory methodology. We applied constant comparative analysis to qualitative data obtained from 12 semi-structured interviews conducted at the Radboud University Medical Center. We used a constructivist approach, in which data and theories are co-created through interaction between the researcher and the field and its participants. We constructed a model for the implementation of medical teaching policy in university hospitals, including five factors that were perceived to promote or inhibit faculty in a university hospital to make use of teaching policy incentives: Executive Board Strategy, Departmental Strategy, Departmental Structure, Departmental Culture, and Individual Strategy. Most factors we found to affect individual teachers' strategies and their use of medical teaching policy lie at the departmental level. If an individual teacher's strategy is focused on medical teaching and a medical teaching career, and the departmental context offers support and opportunity for his/her development, this promotes faculty's use of teaching policy incentives.


Asunto(s)
Educación Médica/organización & administración , Docentes Médicos/organización & administración , Hospitales Universitarios/organización & administración , Políticas , Enseñanza/organización & administración , Educación Médica/economía , Educación Médica/normas , Docentes Médicos/psicología , Docentes Médicos/normas , Consejo Directivo/organización & administración , Teoría Fundamentada , Hospitales Universitarios/economía , Hospitales Universitarios/normas , Humanos , Entrevistas como Asunto , Motivación , Cultura Organizacional , Desarrollo de Personal/organización & administración , Enseñanza/normas
9.
Am J Hum Genet ; 96(4): 532-42, 2015 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-25772935

RESUMEN

Venous thromboembolism (VTE), the third leading cause of cardiovascular mortality, is a complex thrombotic disorder with environmental and genetic determinants. Although several genetic variants have been found associated with VTE, they explain a minor proportion of VTE risk in cases. We undertook a meta-analysis of genome-wide association studies (GWASs) to identify additional VTE susceptibility genes. Twelve GWASs totaling 7,507 VTE case subjects and 52,632 control subjects formed our discovery stage where 6,751,884 SNPs were tested for association with VTE. Nine loci reached the genome-wide significance level of 5 × 10(-8) including six already known to associate with VTE (ABO, F2, F5, F11, FGG, and PROCR) and three unsuspected loci. SNPs mapping to these latter were selected for replication in three independent case-control studies totaling 3,009 VTE-affected individuals and 2,586 control subjects. This strategy led to the identification and replication of two VTE-associated loci, TSPAN15 and SLC44A2, with lead risk alleles associated with odds ratio for disease of 1.31 (p = 1.67 × 10(-16)) and 1.21 (p = 2.75 × 10(-15)), respectively. The lead SNP at the TSPAN15 locus is the intronic rs78707713 and the lead SLC44A2 SNP is the non-synonymous rs2288904 previously shown to associate with transfusion-related acute lung injury. We further showed that these two variants did not associate with known hemostatic plasma markers. TSPAN15 and SLC44A2 do not belong to conventional pathways for thrombosis and have not been associated to other cardiovascular diseases nor related quantitative biomarkers. Our findings uncovered unexpected actors of VTE etiology and pave the way for novel mechanistic concepts of VTE pathophysiology.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Glicoproteínas de Membrana/genética , Proteínas de Transporte de Membrana/genética , Tetraspaninas/genética , Tromboembolia Venosa/genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Oportunidad Relativa
10.
Atherosclerosis ; 238(2): 195-200, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25525746

RESUMEN

OBJECTIVE: Annexin A5 (ANXA5) has been suggested to possess antiatherogenic properties. We investigated whether ANXA5 genetic variations and plasma ANXA5 levels were associated with carotid atherosclerosis and contributed to cardiovascular disease (CVD) risk in patients with familial hypercholesterolemia (FH). METHODS: We sequenced the promoter region and exon 2 of ANXA5 in 284 FH patients from the ASAP (Atorvastatin versus Simvastatin on Atherosclerosis Progression) trial. Common haplotypes (H) were constructed based on seven single nucleotide polymorphisms (SNPs). We studied whether plasma ANXA5 levels or ANXA5 haplotypes were associated with the extent of atherosclerosis (evaluated by carotid intima-media thickness (IMT). The association between ANXA5 haplotypes and the risk for CVD events was investigated in 1730 FH patients from the GIRaFH (Genetic Identification of Risk factors in Familial Hypercholesterolemia) study. RESULTS: In ASAP, individuals carrying the ANXA5 haplotype H2 exhibited lower plasma ANXA5 levels, whereas H4 carriers had increased levels of circulating ANXA5 compared to non-carriers. Plasma ANXA5 levels were not associated with carotid IMT. None of the four ANXA5 haplotypes correlated with the age-related IMT progression (ASAP study) or contributed to CVD risk (GIRaFH cohort). CONCLUSIONS: Both ANXA5 haplotypes and plasma ANXA5 levels were not associated with carotid IMT progression or CVD risk in FH patients.


Asunto(s)
Anexina A5/genética , Enfermedades de las Arterias Carótidas/genética , Grosor Intima-Media Carotídeo , Haplotipos , Hiperlipoproteinemia Tipo II/genética , Polimorfismo de Nucleótido Simple , Factores de Edad , Anciano , Anexina A5/sangre , Biomarcadores/sangre , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/diagnóstico , HDL-Colesterol/sangre , Progresión de la Enfermedad , Exones , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , Masculino , Persona de Mediana Edad , Países Bajos , Fenotipo , Valor Predictivo de las Pruebas , Regiones Promotoras Genéticas , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad
11.
Blood ; 122(18): 3210-9, 2013 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-24014240

RESUMEN

In thrombophilic families, protein S deficiency is clearly associated with venous thrombosis. We aimed to determine whether the same holds true in a population-based case-control study (n = 5317). Subjects were regarded protein S deficient when protein S levels were < 2.5th percentile of the controls. Free and total protein S deficiency was not associated with venous thrombosis: free protein S < 53 U/dL, odds ratio [OR] 0.82 (95% confidence interval [CI], 0.56-1.21) and total protein S < 68 U/dL, OR 0.90 (95% CI, 0.62-1.31). When lower cutoff values were applied, it appeared that subjects at risk of venous thrombosis could be identified at levels < 0.10th percentile of free protein S (< 33 U/dL, OR 5.4; 95% CI, 0.61-48.8). In contrast, even extremely low total protein S levels were not associated with venous thrombosis. PROS1 was sequenced in 48 subjects with free protein S level < 1st percentile (< 4 6 U/dL), and copy number variations were investigated in 2718 subjects, including all subjects with protein S (free or total) < 2.5th percentile. Mutations in PROS1 were detected in 5 patients and 5 controls reinforcing the observation that inherited protein S deficiency is rare in the general population. Protein S testing and PROS1 testing should not be considered in unselected patients with venous thrombosis.


Asunto(s)
Deficiencia de Proteína S/metabolismo , Proteína S/metabolismo , Trombosis de la Vena/metabolismo , Adulto , Anciano , Estudios de Casos y Controles , Variaciones en el Número de Copia de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Oportunidad Relativa , Proteína S/genética , Deficiencia de Proteína S/sangre , Deficiencia de Proteína S/genética , Medición de Riesgo , Factores de Riesgo , Análisis de Secuencia de ADN , Trombosis de la Vena/sangre
12.
Med Teach ; 35(9): e1485-92, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23968325

RESUMEN

BACKGROUND: Physicians play a crucial role in teaching residents in clinical practice. Feedback on their teaching performance to support this role needs to be provided in a carefully designed and constructive way. AIMS: We investigated an evaluation system for evaluating supervisors and providing formative feedback. METHOD: In a design based research approach, the 'Evaluation and Feedback For Effective Clinical Teaching System' (EFFECT-S) was examined by conducting semi-structured interviews with residents and supervisors of five departments in five different hospitals about feedback conditions, acceptance and its effects. Interviews were analysed by three researchers, using qualitative research software (ATLAS-Ti). RESULTS: Principles and characteristics of the design are supported by evaluating EFFECT-S. All steps of EFFECT-S appear necessary. A new step, team evaluation, was added. Supervisors perceived the feedback as instructive; residents felt capable of providing feedback. Creating safety and honesty require different actions for residents and supervisors. Outcomes include awareness of clinical teaching, residents learning feedback skills, reduced hierarchy and an improved learning climate. CONCLUSIONS: EFFECT-S appeared useful for evaluating supervisors. Key mechanism was creating a safe environment for residents to provide honest and constructive feedback. Residents learned providing feedback, being part of the CanMEDS and ACGME competencies of medical education programmes.


Asunto(s)
Educación de Postgrado en Medicina , Evaluación Educacional , Docentes Médicos , Retroalimentación , Internado y Residencia , Adulto , Actitud del Personal de Salud , Comunicación , Femenino , Grupos Focales , Humanos , Masculino
13.
PLoS Genet ; 9(2): e1003266, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23408906

RESUMEN

Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.


Asunto(s)
Hipertiroidismo/genética , Hipotiroidismo/genética , Glándula Tiroides , Tirotropina/genética , Tiroxina/sangre , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Hipertiroidismo/sangre , Hipotiroidismo/sangre , Masculino , Fenotipo , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Caracteres Sexuales , Transducción de Señal/genética , Glándula Tiroides/metabolismo , Glándula Tiroides/fisiopatología , Tirotropina/sangre , Tiroxina/genética
14.
Biostatistics ; 14(2): 220-31, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22989557

RESUMEN

Family studies are often used in genetic research to explore associations between genetic markers and various phenotypes. A commonly used design oversamples families enriched with the disease under study for efficient data collection and estimation. For instance, in a multiple cases family study, families are selected based on the number of affected relatives. In such cases, valid inference for the model parameters relies on the proper modeling of both the within family correlations and the outcome-dependent sampling, also known as ascertainment. A flexible modeling approach is the ascertainment-corrected mixed-effects model, but it is known to only be asymptotically identifiable, because in small samples the available data do not provide sufficient information to estimate both the intercept and the genetic variance. To deal with this issue, we propose a penalized maximum likelihood estimation procedure which reliably estimates the model parameters in small family studies by using external population-based information.


Asunto(s)
Familia , Estudios de Asociación Genética/estadística & datos numéricos , Funciones de Verosimilitud , Sistema del Grupo Sanguíneo ABO/genética , Bioestadística , Interpretación Estadística de Datos , Factor V/genética , Variación Genética , Humanos , Modelos Genéticos , Modelos Estadísticos , Hermanos , Trombosis de la Vena/sangre , Trombosis de la Vena/genética
16.
Nat Genet ; 44(3): 319-22, 2012 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-22267200

RESUMEN

To search for sequence variants conferring risk of nonmedullary thyroid cancer, we focused our analysis on 22 SNPs with a P < 5 × 10(-8) in a genome-wide association study on levels of thyroid stimulating hormone (TSH) in 27,758 Icelanders. Of those, rs965513 has previously been shown to associate with thyroid cancer. The remaining 21 SNPs were genotyped in 561 Icelandic individuals with thyroid cancer (cases) and up to 40,013 controls. Variants suggestively associated with thyroid cancer (P < 0.05) were genotyped in an additional 595 non-Icelandic cases and 2,604 controls. After combining the results, three variants were shown to associate with thyroid cancer: rs966423 on 2q35 (OR = 1.34; P(combined) = 1.3 × 10(-9)), rs2439302 on 8p12 (OR = 1.36; P(combined) = 2.0 × 10(-9)) and rs116909374 on 14q13.3 (OR = 2.09; P(combined) = 4.6 × 10(-11)), a region previously reported to contain an uncorrelated variant conferring risk of thyroid cancer. A strong association (P = 9.1 × 10(-91)) was observed between rs2439302 on 8p12 and expression of NRG1, which encodes the signaling protein neuregulin 1, in blood.


Asunto(s)
Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 2/genética , Cromosomas Humanos Par 8/genética , Sitios Genéticos/genética , Predisposición Genética a la Enfermedad/genética , Neoplasias de la Tiroides/genética , Tirotropina/metabolismo , Variación Genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Islandia , Neurregulina-1/sangre , Neurregulina-1/genética , Polimorfismo de Nucleótido Simple/genética
17.
Nat Genet ; 43(11): 1127-30, 2011 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-21983786

RESUMEN

We tested 16 million SNPs, identified through whole-genome sequencing of 457 Icelanders, for association with gout and serum uric acid levels. Genotypes were imputed into 41,675 chip-genotyped Icelanders and their relatives, for effective sample sizes of 968 individuals with gout and 15,506 individuals for whom serum uric acid measurements were available. We identified a low-frequency missense variant (c.1580C>G) in ALDH16A1 associated with gout (OR = 3.12, P = 1.5 × 10(-16), at-risk allele frequency = 0.019) and serum uric acid levels (effect = 0.36 s.d., P = 4.5 × 10(-21)). We confirmed the association with gout by performing Sanger sequencing on 6,017 Icelanders. The association with gout was stronger in males relative to females. We also found a second variant on chromosome 1 associated with gout (OR = 1.92, P = 0.046, at-risk allele frequency = 0.986) and serum uric acid levels (effect = 0.48 s.d., P = 4.5 × 10(-16)). This variant is close to a common variant previously associated with serum uric acid levels. This work illustrates how whole-genome sequencing data allow the detection of associations between low-frequency variants and complex traits.


Asunto(s)
Gota/genética , Polimorfismo de Nucleótido Simple , Ácido Úrico/sangre , Humanos , Islandia , Mutación Missense
20.
Thromb Haemost ; 101(6): 1078-84, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19492150

RESUMEN

Genetic determinants of venous thromboembolism (VTE) in the African-American population are poorly characterised. It was recently shown that fibrinogen gamma gene (FGG) polymorphisms 10034C>T and 9340T>C influence VTE risk in the Caucasian population. In the African-American population these polymorphisms are common, with allele frequencies above 25%. Here we evaluated whether these and other FGG 3'-end polymorphisms were associated with VTE risk in the African-American population and aimed to replicate the association in the Caucasian population. We examined 557 Caucasian patients and 678 Caucasian controls, and 537 African-American patients and 586 African-American controls from the ;Genetic Attributes and Thrombosis Epidemiology' (GATE) study. In the African-American population, 10034C>T and 9340T>C marginally influenced VTE-risk, with a 20% increase in risk for 10034TT carriers and a 20% reduction in risk for 9340CC carriers. In the Caucasian population, 10034TT was associated with a 1.7-fold increase in risk, which increased to 2.1-fold for idiopathic VTE patients. 9340CC significantly reduced VTE risk approximately two-fold. In conclusion, both FGG polymorphisms 10034C>T and 9340T>C influence VTE-risk, with the strongest effects observed in the Caucasian population, confirming previous data on these polymorphisms in this population.


Asunto(s)
Región de Flanqueo 3'/genética , Negro o Afroamericano , Fibrinógenos Anormales/genética , Predisposición Genética a la Enfermedad , Tromboembolia Venosa/genética , Población Blanca , Adolescente , Adulto , Anciano , Análisis Mutacional de ADN , Femenino , Fibrinógenos Anormales/metabolismo , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/fisiopatología
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