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Chen, C. H., Peng, Q., Schork, A. J., Lo, M. T., Fan, C. C., Wang, Y., et al. (2015). Large-scale genomics unveil polygenic architecture of human cortical surface area. Nature communications, 6, 7549.
Abstract: Little is known about how genetic variation contributes to neuroanatomical variability, and whether particular genomic regions comprising genes or evolutionarily conserved elements are enriched for effects that influence brain morphology. Here, we examine brain imaging and single-nucleotide polymorphisms (SNPs) data from approximately 2,700 individuals. We show that a substantial proportion of variation in cortical surface area is explained by additive effects of SNPs dispersed throughout the genome, with a larger heritable effect for visual and auditory sensory and insular cortices (h(2) approximately 0.45). Genome-wide SNPs collectively account for, on average, about half of twin heritability across cortical regions (N=466 twins). We find enriched genetic effects in or near genes. We also observe that SNPs in evolutionarily more conserved regions contributed significantly to the heritability of cortical surface area, particularly, for medial and temporal cortical regions. SNPs in less conserved regions contributed more to occipital and dorsolateral prefrontal cortices.
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Quanjer, P. H., Ruppel, G. L., Langhammer, A., Krishna, A., Mertens, F., Johannessen, A., et al. (2017). Bronchodilator Response in FVC Is Larger and More Relevant Than in FEV1 in Severe Airflow Obstruction. Chest, 151(5), 1088–1098.
Abstract: BACKGROUND: Recommendations on interpreting tests of bronchodilator responsiveness (BDR) are conflicting. We investigated the dependence of BDR criteria on sex, age, height, ethnicity, and severity of respiratory impairment. METHODS: BDR test data were available from clinical patients in the Netherlands, New Zealand, and the United States (n = 15,278; female subjects, 51.7%) and from surveys in Canada, Norway, and five Latin-American countries (n = 16,250; female subjects, 54.7%). BDR calculated according to FEV1, FVC, and FEV1/FVC was expressed as absolute change, a percentage of the baseline level (% baseline), a percentage of the predicted value (% predicted), and z score. RESULTS: Change (Delta) in FEV1 and FVC, in milliliters, was unrelated to the baseline value but was biased toward age, height, sex, and level of airways obstruction; DeltaFEV1 was significantly lower in African Americans. In 1,106 subjects with low FEV1 (200-1,621 mL) the FEV1 increased by 12% to 44.7% relative to baseline but < 200 mL. Expressing BDR as a percentage of the predicted value or as a z score attenuated the bias and made the 200-mL criterion redundant, but reduced positive responses by half. DeltaFEV1 % baseline increased with the level of airflow obstruction but decreased with severe obstruction when expressed as z scores or % predicted; DeltaFVC, however expressed, increased with the level of airflow obstruction. CONCLUSIONS: Expressing FEV1 responsiveness as % baseline spuriously suggests that responsiveness increases with the severity of respiratory impairment. Expressing change in FEV1 or FVC as % predicted or as z scores eliminates this artifact and renders the required 200-mL minimum increase redundant. In severe airways obstruction DeltaFVC should be critically evaluated as an index of clinically important relief of hyperinflation, with implications for bronchodilator drug trials.
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