Validation of an integrated pedal desk and electronic behavior tracking platform

Background This study tested the validity of revolutions per minute (RPM) measurements from the Pennington Pedal Desk™. Forty-four participants (73 % female; 39 ± 11.4 years-old; BMI 25.8 ± 5.5 kg/m2 [mean ± SD]) completed a standardized trial consisting of guided computer tasks while using a pedal desk for approximately 20 min. Measures of RPM were concurrently collected by the pedal desk and the Garmin Vector power meter. After establishing the validity of RPM measurements with the Garmin Vector, we performed equivalence tests, quantified mean absolute percent error (MAPE), and constructed Bland–Altman plots to assess agreement between RPM measures from the pedal desk and the Garmin Vector (criterion) at the minute-by-minute and trial level (i.e., over the approximate 20 min trial period). Results The average (mean ± SD) duration of the pedal desk trial was 20.5 ± 2.5 min. Measures of RPM (mean ± SE) at the minute-by-minute (Garmin Vector: 54.8 ± 0.4 RPM; pedal desk: 55.8 ± 0.4 RPM) and trial level (Garmin Vector: 55.0 ± 1.7 RPM; pedal desk: 56.0 ± 1.7 RPM) were deemed equivalent. MAPE values for RPM measured by the pedal desk were small (minute-by-minute: 2.1 ± 0.1 %; trial: 1.8 ± 0.1 %) and no systematic relationships in error variance were evident by Bland–Altman plots. Conclusion The Pennington Pedal Desk™ provides a valid count of RPM, providing an accurate metric to promote usage

A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus

Systemic lupus erythematosus (SLE or lupus) (OMIM: 152700) is a chronic autoimmune disease with debilitating inflammation that affects multiple organ systems. The STAT1-STAT4 locus is one of the first and most highly replicated genetic loci associated with lupus risk. We performed a fine-mapping study to identify plausible causal variants within the STAT1-STAT4 locus associated with increased lupus disease risk. Using complementary frequentist and Bayesian approaches in trans-ancestral Discovery and Replication cohorts, we found one variant whose association with lupus risk is supported across ancestries in both the Discovery and Replication cohorts: rs11889341. In B cell lines from patients with lupus and healthy controls, the lupus risk allele of rs11889341 was associated with increased STAT1 expression. We demonstrated that the transcription factor HMGA1, a member of the HMG transcription factor family with an AT-hook DNA-binding domain, has enriched binding to the risk allele compared with the non-risk allele of rs11889341.We identified a genotype-dependent repressive element in the DNA within the intron of STAT4 surrounding rs11889341. Consistent with expression quantitative trait locus (eQTL) analysis, the lupus risk allele of rs11889341 decreased the activity of this putative repressor. Altogether, we present a plausible molecular mechanism for increased lupus risk at the STAT1-STAT4 locus in which the risk allele of rs11889341, the most probable causal variant, leads to elevated STAT1 expression in B cells due to decreased repressor activity mediated by increased binding of HMGA1. © The Author(s) 2018. Published by Oxford University Press. All rights reserved

A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus

Systemic lupus erythematosus (SLE or lupus) (OMIM: 152700) is a chronic autoimmune disease with debilitating inflammation that affects multiple organ systems. The STAT1-STAT4 locus is one of the first and most highly replicated genetic loci associated with lupus risk. We performed a fine-mapping study to identify plausible causal variants within the STAT1-STAT4 locus associated with increased lupus disease risk. Using complementary frequentist and Bayesian approaches in trans-ancestral Discovery and Replication cohorts, we found one variant whose association with lupus risk is supported across ancestries in both the Discovery and Replication cohorts: rs11889341. In B cell lines from patients with lupus and healthy controls, the lupus risk allele of rs11889341 was associated with increased STAT1 expression. We demonstrated that the transcription factor HMGA1, a member of the HMG transcription factor family with an AT-hook DNA-binding domain, has enriched binding to the risk allele compared with the non-risk allele of rs11889341.We identified a genotype-dependent repressive element in the DNA within the intron of STAT4 surrounding rs11889341. Consistent with expression quantitative trait locus (eQTL) analysis, the lupus risk allele of rs11889341 decreased the activity of this putative repressor. Altogether, we present a plausible molecular mechanism for increased lupus risk at the STAT1-STAT4 locus in which the risk allele of rs11889341, the most probable causal variant, leads to elevated STAT1 expression in B cells due to decreased repressor activity mediated by increased binding of HMGA1. © The Author(s) 2018. Published by Oxford University Press. All rights reserved