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Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.
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Estudio de Asociación del Genoma Completo/métodos , Técnicas de Genotipaje/métodos , Genética Humana/métodos , Exactitud de los Datos , Variación Genética , Genética de Población/métodos , Genética de Población/normas , Estudio de Asociación del Genoma Completo/normas , Técnicas de Genotipaje/normas , Genética Humana/normas , Humanos , LinajeRESUMEN
African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multi-generational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within Africa as well as how within-Africa variation can be informative for broader variant interpretation; many variants that are rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity across Africa.
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Variación Genética , Genética de Población , África Austral , Población Negra/genética , Estructuras Genéticas , Variación Genética/genética , HumanosRESUMEN
Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N = 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1 and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.
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INTRODUCTION: Lifestyle factors such as smoking, alcohol use, suboptimal diet, and inadequate physical activity have been associated with increased risk of cardiovascular diseases. There are limited data on these risk factors among patients with psychosis in low- and middle-income countries. OBJECTIVES: This study aimed to establish the prevalence of lifestyle cardiovascular risk factors, and the 10-year cardiovascular risk scores and associated factors in patients with psychosis compared to controls at Moi Teaching and Referral Hospital in Eldoret, Kenya. METHODS: A sample of 297 patients with schizophrenia, schizoaffective disorder, or bipolar mood disorder; and 300 controls matched for age and sex were included in this analysis. A study specific researcher-administered questionnaire was used to collect data on demographics, antipsychotic medication use, smoking, alcohol intake, diet, and physical activity. Weight, height, abdominal circumference, and blood pressure were also collected to calculate the Framingham 10-year Cardiovascular Risk Score (FRS), while blood was drawn for measurement of glucose level and lipid profile. Pearson's chi-squared tests and t-tests were employed to assess differences in cardiovascular risk profiles between patients and controls, and a linear regression model was used to determine predictors of 10-year cardiovascular risk in patients. RESULTS: Compared to controls, patients with psychosis were more likely to have smoked in their lifetimes (9.9% vs. 3.3%, p = 0.006) or to be current smokers (13.8% vs. 7%, p = 0.001). Over 97% of patients with psychosis consumed fewer than five servings of fruits and vegetables per week; 78% engaged in fewer than three days of vigorous exercise per week; and 48% sat for more than three hours daily. The estimated 10-year risk of CVD was relatively low in this study: the FRS in patients was 3.16, compared to 2.93 in controls. The estimated 10-year cardiovascular risk in patients was significantly associated with female sex (p = 0.007), older patients (p < 0.001), current tobacco smoking (p < 0.001), and metabolic syndrome (p < 0.001). CONCLUSION: In the setting of Eldoret, there is suboptimal physical exercise and intake of healthy diet among patients with psychosis and controls. While the estimated risk score among patients is relatively low in our study, these data may be useful for informing future studies geared towards informing interventions to promote healthy lifestyles in this population.
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Enfermedades Cardiovasculares , Trastornos Psicóticos , Humanos , Adulto , Femenino , Factores de Riesgo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Prevalencia , Kenia/epidemiología , Trastornos Psicóticos/epidemiología , Estilo de Vida , Factores de Riesgo de Enfermedad Cardiaca , Hospitales , Derivación y ConsultaRESUMEN
Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.
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Metilación de ADN , Epigenoma , Ansiedad/genética , Metilación de ADN/genética , Epigénesis Genética/genética , Epigenómica , Femenino , Humanos , EmbarazoRESUMEN
INTRODUCTION: Indoor air pollution and maternal smoking during pregnancy are associated with respiratory symptoms in infants, but little is known about the direct association with lung function or interactions with genetic risk factors. We examined associations of exposure to indoor particulate matter with a 50% cut-off aerodynamic diameter of 10â µm (PM10) and maternal smoking with infant lung function and the role of gene-environment interactions. METHODS: Data from the Drakenstein Child Health Study, a South African birth cohort, were analysed (n=270). Lung function was measured at 6â weeks and 1â year of age, and lower respiratory tract infection episodes were documented. We measured pre- and postnatal PM10 exposures using devices placed in homes, and prenatal tobacco smoke exposure using maternal urine cotinine levels. Genetic risk scores determined from associations with childhood-onset asthma in the UK Biobank were used to investigate effect modifications. RESULTS: Pre- and postnatal exposure to PM10 as well as maternal smoking during pregnancy were associated with reduced lung function at 6â weeks and 1â year as well as with lower respiratory tract infection in the first year. Due to a significant interaction between the genetic risk score and prenatal exposure to PM10, infants carrying more asthma-related risk alleles were more susceptible to PM10-associated reduced lung function (pinteraction=0.007). This interaction was stronger in infants with Black African ancestry (pinteraction=0.001) and nonexistent in children with mixed ancestry (pinteraction=0.876). CONCLUSIONS: PM10 and maternal smoking exposures were associated with reduced lung function, with a higher susceptibility for infants with an adverse genetic predisposition for asthma that also depended on the infant's ancestry.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Contaminación del Aire , Asma , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Contaminación del Aire Interior/efectos adversos , Contaminación del Aire Interior/análisis , Asma/etiología , Asma/genética , Niño , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lactante , Material Particulado/efectos adversos , Material Particulado/análisis , EmbarazoRESUMEN
BACKGROUND: Approximately 250 million (43%) children under the age of 5 years in low- and middle-income countries (LMICs) are failing to meet their developmental potential. Risk factors are recognised to contribute to this loss of human potential. Expanding understanding of the risks that lead to poor outcomes and which protective factors contribute to resilience in children may be critical to improving disparities. METHODS AND FINDINGS: The Drakenstein Child Health Study is a population-based birth cohort in the Western Cape, South Africa. Pregnant women were enrolled between 20 and 28 weeks' gestation from two community clinics from 2012 to 2015; sociodemographic and psychosocial data were collected antenatally. Mothers and children were followed through birth until 2 years of age. Developmental assessments were conducted by trained assessors blinded to background, using the Bayley-III Scales of Infant and Toddler Development (BSID-III), validated for use in South Africa, at 24 months of age. The study assessed all available children at 24 months; however, some children were not able to attend, because of loss to follow-up or unavailability of a caregiver or child at the correct age. Of 1,143 live births, 1,002 were in follow-up at 24 months, and a total of 734 children (73%) had developmental assessments, of which 354 (48.2%) were girls. This sample was characterised by low household employment (n = 183; 24.9%) and household income (n = 287; 39.1% earning
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Conducta Infantil , Desarrollo Infantil , Discapacidades del Desarrollo/epidemiología , Determinantes Sociales de la Salud , Factores Socioeconómicos , Factores de Edad , Peso al Nacer , Preescolar , Discapacidades del Desarrollo/fisiopatología , Discapacidades del Desarrollo/prevención & control , Discapacidades del Desarrollo/psicología , Escolaridad , Femenino , Humanos , Masculino , Salud Materna , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Sudáfrica/epidemiologíaRESUMEN
Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We applied transcriptome-wide screens to 149 umbilical cord blood samples from neonates born to mothers with posttraumatic stress disorder (PTSD; nâ¯=â¯20), depression (nâ¯=â¯31) and PTSD with comorbid depression (nâ¯=â¯13), compared to carefully matched trauma exposed controls (nâ¯=â¯23) and healthy mothers (nâ¯=â¯62). Analyses by maternal diagnoses revealed a clear pattern of gene expression signatures distinguishing neonates born to mothers with a history of psychopathology from those without. Co-expression network analysis identified distinct gene expression perturbations across maternal diagnoses, including two depression-related modules implicated in axon-guidance and mRNA stability, as well as two PTSD-related modules implicated in TNF signaling and cellular response to stress. Notably, these disease-related modules were enriched with brain-expressed genes and genetic risk loci for autism spectrum disorder and schizophrenia, which may imply a causal role for impaired developmental outcomes. These molecular alterations preceded changes in clinical measures at twenty-four months, including reductions in cognitive and socio-emotional outcomes in affected infants. Collectively, these findings indicate that prenatal exposure to maternal psychological distress induces neuronal, immunological and behavioral abnormalities in affected offspring and support the search for early biomarkers of exposures to adverse in utero environments and the classification of children at risk for impaired development.
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Trastornos del Neurodesarrollo/genética , Efectos Tardíos de la Exposición Prenatal/genética , Estrés Psicológico/genética , Adulto , Trastorno del Espectro Autista/genética , Cordocentesis/métodos , Depresión/fisiopatología , Depresión/psicología , Femenino , Sangre Fetal/metabolismo , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Madres/psicología , Trastornos del Neurodesarrollo/etiología , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Factores de Riesgo , Esquizofrenia/genética , Sudáfrica , Trastornos por Estrés Postraumático/fisiopatología , Trastornos por Estrés Postraumático/psicología , Estrés Psicológico/fisiopatología , Transcriptoma/genéticaRESUMEN
BACKGROUND: Cohort studies have noted associations between hazardous alcohol use during pregnancy and infant growth outcomes, but many have not controlled for potential psychosocial confounders. To assess the unique contribution of hazardous alcohol use, we examined its effect on infant growth outcomes while controlling for maternal psychosocial stressors and hazardous tobacco and drug use in a cohort of 986 pregnant South African women enrolled into the Drakenstein Child Health Study between 2012 and 2015. METHODS: Data on psychosocial stressors and maternal risk behaviors were collected between 28 and 32 weeks of gestation. Participants were categorized as hazardous alcohol users if they obtained moderate or high scores (>10) on the Alcohol, Smoking and Substance Involvement Screening Test at this assessment or retrospectively reported drinking at least 2 drinks weekly during any trimester of pregnancy. Infant growth outcomes were recorded at delivery. Multivariable regression models examined correlates of hazardous alcohol use and associations between hazardous alcohol use and birth outcomes. RESULTS: Overall, 13% of mothers reported hazardous alcohol use. Recent exposure to intimate partner violence (adjusted odds ratio (aOR) = 2.08; 95% confidence interval (CI): 1.37, 3.18) and hazardous tobacco use (aOR = 5.03; 95% CI: 2.97, 8.52) were significant correlates of hazardous alcohol use. After controlling for potential psychosocial confounders, hazardous alcohol use remained associated with lower infant weight-for-age (B = -0.35, 95% CI: -0.56, -0.14), height-for-age (B = -0.46, 95% CI: -0.76, -0.17), and head-circumference-for-age z-scores (B = -0.43, 95% CI: -0.69, -0.17). CONCLUSIONS: Interventions to reduce hazardous alcohol use among pregnant women in South Africa are needed to prevent alcohol-related infant growth restrictions. As these growth deficits may lead to neurodevelopmental consequences, it is critical to identify alcohol-related growth restrictions at birth and link exposed infants to early interventions for neurodevelopment.
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Consumo de Bebidas Alcohólicas/epidemiología , Fumar Cigarrillos/epidemiología , Retardo del Crecimiento Fetal/epidemiología , Violencia de Pareja/estadística & datos numéricos , Complicaciones del Embarazo/epidemiología , Estrés Psicológico/epidemiología , Adulto , Peso al Nacer , Estudios de Cohortes , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Masculino , Análisis Multivariante , Oportunidad Relativa , Embarazo , Sudáfrica/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Low lung function in early life is associated with later respiratory illness. There is limited data on lung function in African infants despite a high prevalence of respiratory disease. AIM: To assess the determinants of early lung function in African infants. METHOD: Infants enrolled in a South African birth cohort, the Drakenstein child health study, had lung function measured at 6-10â weeks of age. Measurements, made with the infant breathing via a facemask during natural sleep, included tidal breathing, sulfur hexafluoride multiple breath washout and the forced oscillation technique. Information on antenatal and early postnatal exposures was collected using questionnaires and urine cotinine. Household benzene exposure was measured antenatally. RESULTS: Successful tests were obtained in 645/675 (95%) infants, median (IQR) age of 51 (46-58)â days. Infant size, age and male gender were associated with larger tidal volume. Infants whose mothers smoked had lower tidal volumes (-1.6â mL (95% CI -3.0 to -0.1), p=0.04) and higher lung clearance index (0.1 turnovers (95% CI 0.01 to 0.3), p=0.03) compared with infants unexposed to tobacco smoke. Infants exposed to alcohol in utero or household benzene had lower time to peak tidal expiratory flow over total expiratory time ratios, 10% (95% CI -15.4% to -3.7%), p=0.002) and 3.0% (95% CI -5.2% to -0.7%, p=0.01) lower respectively compared with unexposed infants. HIV-exposed infants had higher tidal volumes (1.7â mL (95% CI 0.06 to 3.3) p=0.04) compared with infants whose mothers were HIV negative. CONCLUSION: We identified several factors including infant size, sex, maternal smoking, maternal alcohol, maternal HIV and household benzene associated with altered early lung function, many of which are factors amenable to public health interventions. Long-term study of lung function and respiratory disease in these children is a priority to develop strategies to strengthen child health.
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Pulmón/fisiopatología , Pruebas de Función Respiratoria/métodos , Benceno/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Humanos , Lactante , Masculino , Intercambio Materno-Fetal , Embarazo , Efectos Tardíos de la Exposición Prenatal , Factores de Riesgo , Factores Sexuales , Sudáfrica , Encuestas y CuestionariosRESUMEN
BACKGROUND: There is growing evidence of the negative impact of alcohol on morbidity and mortality of individuals living with HIV but limited evidence of in utero effects of HIV and alcohol on exposure on infants. METHODS: We conducted a population-based birth cohort study (N = 667 mother-infant dyads) in South Africa to investigate whether maternal alcohol use and HIV affected gestational outcomes. Descriptive data analysis was conducted for all variables using frequency distributions, measures of central tendency, and estimates of variance. Hierarchical multiple regression was conducted to determine whether maternal alcohol use, maternal HIV status and other risk factors (socioeconomic status, smoking, depression) predicted infant outcomes. RESULTS: Our results showed severity of recent alcohol use and lifetime alcohol use predicted low birth weight. Similarly lifetime alcohol use predicted shorter infant length, smaller head length, smaller head circumference, and early gestational age. However, HIV status was not a significant predictor of gestational outcomes. CONCLUSIONS: The unexpected finding that maternal HIV status did not predict any of the gestational outcomes may be due to high rates of ART usage among HIV-infected mothers. The potentially negative effects of HIV on gestational outcomes may have been attenuated by improved maternal health due to high coverage of antiretroviral treatment in South Africa. Interventions are needed to reduce alcohol consumption among pregnant mothers and to support healthy growth and psychosocial development of infants.
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Consumo de Bebidas Alcohólicas/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Trastornos del Espectro Alcohólico Fetal/diagnóstico , Retardo del Crecimiento Fetal/inducido químicamente , Infecciones por VIH/tratamiento farmacológico , Recién Nacido de Bajo Peso , Femenino , Humanos , Lactante , Embarazo , SudáfricaRESUMEN
BACKGROUND: Children exposed to alcohol in utero demonstrate reduced white matter microstructural integrity. While early evidence suggests altered functional brain connectivity in the lateralization of motor networks in school-age children with prenatal alcohol exposure (PAE), the specific effects of alcohol exposure on the establishment of intrinsic connectivity in early infancy have not been explored. METHODS: Sixty subjects received functional imaging at 2 to 4 weeks of age for 6 to 8 minutes during quiet natural sleep. Thirteen alcohol-exposed (PAE) and 14 age-matched control (CTRL) participants with usable data were included in a multivariate model of connectivity between sensorimotor intrinsic functional connectivity networks. Seed-based analyses of group differences in interhemispheric connectivity of intrinsic motor networks were also conducted. The Dubowitz neurological assessment was performed at the imaging visit. RESULTS: Alcohol exposure was associated with significant increases in connectivity between somatosensory, motor networks, brainstem/thalamic, and striatal intrinsic networks. Reductions in interhemispheric connectivity of motor and somatosensory networks did not reach significance. CONCLUSIONS: Although results are preliminary, findings suggest PAE may disrupt the temporal coherence in blood oxygenation utilization in intrinsic networks underlying motor performance in newborn infants. Studies that employ longitudinal designs to investigate the effects of in utero alcohol exposure on the evolving resting-state networks will be key in establishing the distribution and timing of connectivity disturbances already described in older children.
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Consumo de Bebidas Alcohólicas/fisiopatología , Encéfalo/fisiopatología , Complicaciones del Embarazo/fisiopatología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Tronco Encefálico/fisiopatología , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Lateralidad Funcional/fisiología , Neuroimagen Funcional , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Análisis Multivariante , Neostriado/fisiopatología , Vías Nerviosas , Embarazo , Tálamo/fisiopatologíaRESUMEN
Neuroimaging studies have indicated that prenatal alcohol exposure is associated with alterations in the structure of specific brain regions. However, the temporal specificity of such changes and their behavioral consequences are less known. Here we explore the brain structure of infants with in utero exposure to alcohol shortly after birth. T2 structural MRI images were acquired from 28 alcohol-exposed infants and 45 demographically matched healthy controls at 2-4 weeks of age on a 3T Siemens Allegra system as part of large birth cohort study, the Drakenstein Child Health Study (DCHS). Neonatal neurobehavior was assessed at this visit; early developmental outcome assessed on the Bayley Scales of Infant Development III at 6 months of age. Volumes of gray matter regions were estimated based on the segmentations of the University of North Carolina neonatal atlas. Significantly decreased total gray matter volume was demonstrated for the alcohol-exposed cohort compared to healthy control infants (p < 0.001). Subcortical gray matter regions that were significantly different between groups after correcting for overall gray matter volume included left hippocampus, bilateral amygdala and left thalamus (p < 0.01). These findings persisted even when correcting for infant age, gender, ethnicity and maternal smoking status. Both early neurobehavioral and developmental adverse outcomes at 6 months across multiple domains were significantly associated with regional volumes primarily in the temporal and frontal lobes in infants with prenatal alcohol exposure. Alcohol exposure during the prenatal period has potentially enduring neurobiological consequences for exposed children. These findings suggest the effects of prenatal alcohol exposure on brain growth is present very early in the first year of life, a period during which the most rapid growth and maturation occurs.
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Depresores del Sistema Nervioso Central/efectos adversos , Etanol/efectos adversos , Feto/efectos de los fármacos , Sustancia Gris/efectos de los fármacos , Sustancia Gris/patología , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Desarrollo Infantil/efectos de los fármacos , Estudios de Cohortes , Femenino , Sustancia Gris/crecimiento & desarrollo , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal , Caracteres Sexuales , Fumar/efectos adversos , Factores Socioeconómicos , SudáfricaRESUMEN
BACKGROUND: Maternal antenatal depression may be particularly prevalent in low- and middle-income countries, but there is a paucity of data on its effect on birth outcomes in such settings. We investigated risk factors for antenatal depression and the associations between depression and infant birth outcomes in the Drakenstein Child Health Study (DCHS), a birth cohort study in the Western Cape, South Africa. METHODS: The prevalence of depression in pregnant women enrolled in the DCHS from primary care antenatal clinics was measured using the Beck Depression Inventory (BDI-II). Predictors of antenatal depression were investigated using logistic regression, and the associations between depression and infant birth outcomes were examined in linear regression models. RESULTS: Among 726 pregnant women (median age: 26 years), 156 (21%) had BDI-II scores suggesting depression. Independent predictors of depression included single marital status, low socioeconomic status (SES), recent stressful life events, unplanned pregnancy, childhood trauma, and past-year intimate partner violence. No association was observed between antenatal depression and preterm birth. Strong associations were observed between antenatal depression and decreased infant weight-for-age (WAZ) and head circumference-for-age (HCAZ) z-scores at birth. In multivariable analysis, the association between depression and decreased HCAZ remained significant, when adjusted for clinic, SES, and recent stressful life events. CONCLUSIONS: Antenatal depression and associated risk factors are highly prevalent in this setting and are associated with adverse fetal growth. Maternal mental health may be an important predictor of infant growth in utero.
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Depresión/epidemiología , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Resultado del Embarazo/psicología , Mujeres Embarazadas/psicología , Adulto , Depresión/etiología , Depresión/prevención & control , Femenino , Humanos , Recién Nacido , Embarazo , Complicaciones del Embarazo/prevención & control , Complicaciones del Embarazo/psicología , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Factores Socioeconómicos , Sudáfrica/epidemiología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Neuroimaging studies have indicated that prenatal alcohol exposure is associated with alterations in the structure of specific brain regions in children. However, the temporal and regional specificity of such changes and their behavioural consequences are less known. Here we explore the integrity of regional white matter microstructure in infants with in utero exposure to alcohol, shortly after birth. METHODS: Twenty-eight alcohol-exposed and 28 healthy unexposed infants were imaged using diffusion tensor imaging sequences to evaluate white matter integrity using validated tract-based spatial statistics analysis methods. Second, diffusion values were extracted for group comparisons by regions of interest. Differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity were compared between groups and associations with measures from the Dubowitz neonatal neurobehavioural assessment were examined. RESULTS: Lower AD values (p<0.05) were observed in alcohol-exposed infants in the right superior longitudinal fasciculus compared with non-exposed infants. Altered FA and MD values in alcohol-exposed neonates in the right inferior cerebellar were associated with abnormal neonatal neurobehaviour. CONCLUSION: These exploratory data suggest that prenatal alcohol exposure is associated with reduced white matter microstructural integrity even early in the neonatal period. The association with clinical measures reinforces the likely clinical significance of this finding. The location of the findings is remarkably consistent with previously reported studies of white matter structural deficits in older children with a diagnosis of foetal alcohol spectrum disorders.
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Consumo de Bebidas Alcohólicas/efectos adversos , Etanol/envenenamiento , Trastornos del Espectro Alcohólico Fetal/patología , Efectos Tardíos de la Exposición Prenatal , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/patología , Cerebelo/patología , Preescolar , Estudios de Cohortes , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Intercambio Materno-Fetal , EmbarazoRESUMEN
Violence against women is a global public health problem. Exposure to intimate partner violence (IPV) during pregnancy has been associated with a number of adverse maternal and fetal outcomes, including delivery of a low birthweight (LBW) infant. However, there is a paucity of data from low-middle income countries (LMIC). We examined the association between antenatal IPV and subsequent LBW in a South African birth cohort. This study reports data from the Drakenstein Child Lung Health Study (DCLHS), a multidisciplinary birth cohort investigation of the influence of a number of antecedent risk factors on maternal and infant health outcomes over time. Pregnant women seeking antenatal care were recruited at two different primary care clinics in a low income, semi-rural area outside Cape Town, South Africa. Antenatal trauma exposure was assessed using the Childhood Trauma Questionnaire (CTQ) and an IPV assessment tool specifically designed for the purposes of this study. Potential confounding variables including maternal sociodemographics, pregnancy intention, partner support, biomedical and mental illness, substance use and psychosocial risk were also assessed. Bivariate and multiple regression analyses were performed to determine the association between IPV during pregnancy and delivery of an infant with LBW and/or low weight-for-age z (WAZ) scores. The final study sample comprised 263 mother-infant dyads. In multiple regression analyses, the model run was significant [r2 = 0.14 (adjusted r2 = 0.11, F(8, 212) = 4.16, p = 0.0001]. Exposure to physical IPV occurring during the past year was found to be significantly associated with LBW [t = -2.04, p = 0.0429] when controlling for study site (clinic), maternal height, ethnicity, socioeconomic status, substance use and childhood trauma. A significant association with decreased WAZ scores was not demonstrated. Exposure of pregnant women to IPV may impact newborn health. Further research is needed in this field to assess the relevant underlying mechanisms, to inform public health policies and to develop appropriate trauma IPV interventions for LMIC settings.
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Maltrato a los Niños/tendencias , Recién Nacido de Bajo Peso/fisiología , Maltrato Conyugal/tendencias , Adolescente , Adulto , Maltrato a los Niños/economía , Maltrato a los Niños/psicología , Estudios de Cohortes , Femenino , Humanos , Recién Nacido de Bajo Peso/psicología , Recién Nacido , Masculino , Embarazo , Factores de Riesgo , Factores Socioeconómicos , Sudáfrica/epidemiología , Maltrato Conyugal/economía , Maltrato Conyugal/psicología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Background: Incorporating genomic data into risk prediction has become an increasingly useful approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not. Methods: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts. Results: The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy = 89%) using 3728 features and MoRSAE (accuracy = 84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta = 0.6839, p-0.003), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta = 1.92; MoRS, beta = 1.99 and MoRSAE, beta = 1.77) displayed a significant (p < 0.001) predictive power for post-deployment PTSD. Conclusion: Results, especially those from the eMRS, reinforce earlier findings that methylation and trauma are interconnected and can be leveraged to increase the correct classification of those with vs. without PTSD. Moreover, our models can potentially be a valuable tool in predicting the future risk of developing PTSD. As more data become available, including additional molecular, environmental, and psychosocial factors in these scores may enhance their accuracy in predicting the condition and, relatedly, improve their performance in independent cohorts.
RESUMEN
Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.
Asunto(s)
Trastorno Depresivo Mayor , Estudio de Asociación del Genoma Completo , Humanos , Predisposición Genética a la Enfermedad , Trastorno Depresivo Mayor/genética , Depresión , Mapeo Cromosómico , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults. To bridge this gap, we established the Methylation, Imaging and NeuroDevelopment (MIND) Consortium, which aims to bring a developmental focus to the emerging field of Neuroimaging Epigenetics by (i) promoting collaborative, adequately powered developmental research via multi-cohort analyses; (ii) increasing scientific rigor through the establishment of shared pipelines and open science practices; and (iii) advancing our understanding of DNA methylation-brain dynamics at different developmental periods (from birth to emerging adulthood), by leveraging data from prospective, longitudinal pediatric studies. MIND currently integrates 15 cohorts worldwide, comprising (repeated) measures of DNA methylation in peripheral tissues (blood, buccal cells, and saliva) and neuroimaging by magnetic resonance imaging across up to five time points over a period of up to 21 years (Npooled DNAm = 11,299; Npooled neuroimaging = 10,133; Npooled combined = 4,914). By triangulating associations across multiple developmental time points and study types, we hope to generate new insights into the dynamic relationships between peripheral DNA methylation and the brain, and how these ultimately relate to neurodevelopmental and psychiatric phenotypes.