Genome-wide association and functional follow-up reveals new loci for kidney function

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

Does diet affect breast cancer risk?

The role of specific dietary factors in breast cancer causation is not completely resolved. Results from prospective studies do not support the concept that fat intake in middle life has a major relation to breast cancer risk. However, weight gain in middle life contributes substantially to breast cancer risk. Alcohol is the best established dietary risk factor, probably by increasing endogenous estrogen levels. Hypotheses relating diet during youth to risk decades later will be difficult to test. Nevertheless, available evidence is strong that breast cancer risk can be reduced by avoiding weight gain during adult years, and by limiting alcohol consumption

Percepção viso-motora de escolares com Transtorno do Déficit de Atenção com Hiperatividade

PURPOSE: The aim of this study was to characterize and to compare the visual-motor perception of students with Attention Deficit with Hyperactivity Disorder (ADHD) with students with good academic performance. METHODS: Forty students from 2nd to 5th grades of an elementary public school, male gender (100%), aged between 7 and 10 years and 8 months old participated, divided into: GI (20 students with ADHD) and GII (20 students with good academic performance), paired according to age, schooling and gender with GI. The students were submitted to Developmental Test of Visual Perception (DTVP-2). RESULTS: The students of GI presented low performance in spatial position and visual closure (reduced motor) and inferior age equivalent in reduced motor perception, when compared to GII. CONCLUSION: The difficulties in visual-motor perception presented by students of GI cannot be attributed to a primary deficit, but to a secondary phenomenon of inattention that interferes directly in their visual-motor performance.OBJETIVO: Caracterizar e comparar as habilidades de percepção viso-motoras de escolares com Transtorno do Déficit de Atenção com Hiperatividade (TDAH) com escolares com bom desempenho acadêmico. MÉTODOS: Participaram deste estudo 40 escolares na faixa etária de 7 anos a 10 anos e 8 meses, do 2º ao 5º ano do Ensino Fundamental de escolas públicas, divididos em GI (20 escolares com diagnóstico interdisciplinar de TDAH) do gênero masculino (100%) e GII (20 escolares com bom desempenho escolar), pareados com o GI em idade, escolaridade e gênero. Os escolares foram submetidos ao Teste Evolutivo de Percepção Visual (DTVP-2). RESULTADOS: Os escolares de GI apresentaram desempenho inferior na função de posição no espaço e closura visual (motricidade reduzida) e equivalente de idade inferior para percepção de motricidade reduzida em relação ao GII. CONCLUSÃO: As dificuldades em percepção viso-motora apresentadas pelos escolares de GI podem ser atribuídas não a um déficit primário, mas a um fenômeno secundário à desatenção que interfere de forma direta em seu desempenho de percepção viso-motora.Universidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Filosofia e Ciências Departamento de FonoaudiologiaUniversidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Filosofia e CiênciasUniversidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Filosofia e Ciências Departamento de FonoaudiologiaUniversidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Filosofia e Ciência

Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets

Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis

Hypothalamic neurons expressing the anorectic peptide Pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here, we show that Steroid Receptor Coactivator-1 (SRC-1) interacts with a target of leptin receptor activation, phosphorylated STAT3, to potentiate Pomc transcription. Deletion of SRC-1 in Pomc neurons in mice attenuates their depolarization by leptin, decreases Pomc expression and increases food intake leading to high-fat diet-induced obesity. In humans, fifteen rare heterozygous variants in SRC-1 found in severely obese individuals impair leptin-mediated Pomc reporter activity in cells, whilst four variants found in non-obese controls do not. In a knock-in mouse model of a loss of function human variant (SRC-1L1376P), leptin-induced depolarization of Pomc neurons and Pomc expression are significantly reduced, and food intake and body weight are increased. In summary, we demonstrate that SRC-1 modulates the function of hypothalamic Pomc neurons, and suggest that targeting SRC-1 may represent a useful therapeutic strategy for weight loss.Peer reviewe

Author Correction: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps

Correction to: Nature Genetics https://doi.org/10.1038/ng.3668, published online 26 September 2016. In the version of the article published, the surname of author Aaron Isaacs is misspelled as Issacs