Effects of atomoxetine on growth in children with attention-deficit/hyperactivity disorder following up to five years of treatment.

OBJECTIVE: To examine the effects on growth of long-term pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), we present findings from an ongoing 5-year study of the efficacy and safety of treatment with atomoxetine. METHODS: North American patients, 6-17 years old at study entry (N = 1,312) and with Diagnostic and Statistical Manual of Mental Disorders,4th edition (DSM-IV) ADHD, were studied under open-label atomoxetine treatment. Sixty-one were studied up to 5 years. RESULTS: After 1 month\u27s treatment, patients weighed less than expected from their starting percentiles relative to population norms, with a maximum shortfall at 15 months and a return to expected weight by 36 months. Patients were slightly shorter than expected after 12 months, reaching a maximum shortfall at 18 months and returning to expected height by 24 months. Patients in the top quartile for body mass index (BMI) or weight at baseline, and those in the third quartile for height, showed 5-year decreases from expected values. Those below median height at baseline showed increases relative to expected values. CONCLUSIONS: These interim results indicate that continuous atomoxetine treatment for up to 5 years has little or no long-term effect on juvenile growth and final stature for most patients, although persistent decreases from expected may occur in some patients who are larger than average before treatment

Atomic Resonance and Scattering

Contains reports on six research projects.National Science Foundation (PHY83-06273)Joint Services Electronics Program (DAAL03-86-K-0002)National Science Foundation (PHY84-11483)U.S. Navy-Office of Naval Research (Grant N00014-79-C-0183)Joint Services Electronics Program (Contract DAAG29-83-K-0003)National Science Foundation (Grant PHY83-07172-A01)U.S. Navy - Office of Naval Research (Grant N00014-83-K-0695)National Science Foundation (Grant CHE84-21392

Latitude, digit ratios, and Allen's and Bergmann's rules: a comment on Loehlin, McFadden, Medland, and Martin (2006)

Comments on an article by J. C. Loehlin, D. McFadden, S. E. Medland and N. G. Martin (see record 2007-07455-014). The authors investigated the relationship between latitude and digit ratio (2D:4D). Like digit ratio, height has been suggested to reflect physical masculinization. Height is also positively correlated with perceptual-verbal ability (in women) and mental rotation ability. Latitude effect may not be completely independent of the hypothesized organizational effects of testosterone. Sex ratios appear to be influenced by circulating hormone levels in the parents around the time of conception and sex ratios at birth appear to be male-biased towards the equator and relatively male-biased at high latitudes. Regardless, any link between organizational testosterone and stature on the one hand and digit ratio on the other, and inter-ethnic variation in all three physical traits, requires further investigation. We suggest that much of the variance in digit ratio attributable to latitude is actually due to an allometric relationship between body size and digit ratio across populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83881/1/latitude_digit_ratios_a_comment_on_loehlin.pd

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

The genomics of heart failure: design and rationale of the HERMES consortium

Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.</p

The genomics of heart failure: design and rationale of the HERMES consortium

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome‐wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow‐up following heart failure diagnosis ranged from 2 to 116 months. Forty‐nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low‐frequency variants (allele frequency 0.01–0.05) at P &lt; 5 × 10−8 under an additive genetic model. Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction