ORDINARY LEAST SQUARES REGRESSION OF ORDERED CATEGORICAL DATA: INFERENTIAL IMPLICATIONS FOR PRACTICE

Ordered categorical responses (OCRs) are frequently encountered in many disciplines. Examples of interest in agriculture include quality assessments, such as for soil or food products, and evaluation of lesion severity, such as teat ends status in dairy cattle. OCRs are characterized by multiple categories recorded on a ranked scale that, while apprising relative order, is not informative of absolute magnitude of or proportionality between the categories. A number of statistically sound models for OCRs are available in the statistical literature, such as logistic regression and probit models, but these are commonly underutilized in practice. Instead, the ordinary least squares linear regression (OLSLR) model is often employed despite violation of basic model assumptions. In this study, the inferential implications of OLSLR-based inference on OCRs were investigated using a simulation study that evaluated realized Type I error rate and empirical statistical power. The design of the simulation study was motivated by applications reported in the subject-matter literature. A variety of plausible scenarios were considered for simulation, including various shapes of the frequency distribution and number of categories of the OCR. Using survey data on frequency of antimicrobial use in cattle feedlots, we illustrated the inferential performance of OLSLR on OCRs relative to a probit model

Bipolar disorder with binge eating behavior: a genome-wide association study implicates PRR5-ARHGAP8

Bipolar disorder (BD) is associated with binge eating behavior (BE), and both conditions are heritable. Previously, using data from the Genetic Association Information Network (GAIN) study of BD, we performed genome-wide association (GWA) analyses of BD with BE comorbidity. Here, utilizing data from the Mayo Clinic BD Biobank (969 BD cases, 777 controls), we performed a GWA analysis of a BD subtype defined by BE, and case-only analysis comparing BD subjects with and without BE. We then performed a meta-analysis of the Mayo and GAIN results. The meta-analysis provided genome-wide significant evidence of association between single nucleotide polymorphisms (SNPs) in PRR5-ARHGAP8 and BE in BD cases (rs726170 OR=1.91, P=3.05E-08). In the meta-analysis comparing cases with BD with comorbid BE vs. non-BD controls, a genome-wide significant association was observed at SNP rs111940429 in an intergenic region near PPP1R2P5 (p=1.21E-08). PRR5-ARHGAP8 is a read-through transcript resulting in a fusion protein of PRR5 and ARHGAP8. PRR5 encodes a subunit of mTORC2, a serine/threonine kinase that participates in food intake regulation, while ARHGAP8 encodes a member of the RhoGAP family of proteins that mediate cross-talk between Rho GTPases and other signaling pathways. Without BE information in controls, it is not possible to determine whether the observed association reflects a risk factor for BE in general, risk for BE in individuals with BD, or risk of a subtype of BD with BE. The effect of PRR5-ARHGAP8 on BE risk thus warrants further investigation

Blood transfusion history and risk of non-Hodgkin lymphoma : an InterLymph pooled analysis

PURPOSE: To conduct a pooled analysis assessing the association of blood transfusion with risk of non-Hodgkin lymphoma (NHL). METHODS: We used harmonized data from 13 case-control studies (10,805 cases, 14,026 controls) in the InterLymph Consortium. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, adjusted for study design variables. RESULTS: Among non-Hispanic whites (NHW), history of any transfusion was inversely associated with NHL risk for men (OR 0.74; 95% CI 0.65-0.83) but not women (OR 0.92; 95% CI 0.83-1.03), pheterogeneity = 0.014. Transfusion history was not associated with risk in other racial/ethnic groups. There was no trend with the number of transfusions, time since first transfusion, age at first transfusion, or decade of first transfusion, and further adjustment for socioeconomic status, body mass index, smoking, alcohol use, and HCV seropositivity did not alter the results. Associations for NHW men were stronger in hospital-based (OR 0.56; 95% CI 0.45-0.70) but still apparent in population-based (OR 0.84; 95% CI 0.72-0.98) studies. CONCLUSIONS: In the setting of a literature reporting mainly null and some positive associations, and the lack of a clear methodologic explanation for our inverse association restricted to NHW men, the current body of evidence suggests that there is no association of blood transfusion with risk of NHL

Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = −0.14; 95% confidence interval [CI]: −0.24 to −0.03; p value = 0.010) and MDD (β = −0.16; 95% CI: −0.27 to −0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34–1.93; p value = 2e−7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD

Ordinary least squares regression of ordered categorical data: inferential implications for practice

Master of ScienceDepartment of StatisticsNora BelloOrdered categorical responses are frequently encountered in many disciplines. Examples of interest in agriculture include quality assessments, such as for soil or food products, and evaluation of lesion severity, such as teat ends status in dairy cattle. Ordered categorical responses are characterized by multiple categories or levels recorded on a ranked scale that, while apprising relative order, are not informative of magnitude of or proportionality between levels. A number of statistically sound models for ordered categorical responses have been proposed, such as logistic regression and probit models, but these are commonly underutilized in practice. Instead, the ordinary least squares linear regression model is often employed with ordered categorical responses despite violation of basic model assumptions. In this study, the inferential implications of this approach are investigated using a simulation study that evaluates robustness based on realized Type I error rate and statistical power. The design of the simulation study is motivated by applied research cases reported in the literature. A variety of plausible scenarios were considered for simulation, including various shapes of the frequency distribution and different number of categories of the ordered categorical response. Using a real dataset on frequency of antimicrobial use in feedlots, I demonstrate the inferential performance of ordinary least squares linear regression on ordered categorical responses relative to a probit model

A Digital Health Weight Loss Program in 250,000 Individuals

Importance. Obesity is a worsening epidemic worldwide. Effective and accessible weight loss programs to combat obesity on a large scale are warranted, but a need for frequent face-to-face care might impose a limitation. Objective. To evaluate whether individuals following a weight loss program based on a mobile application, wireless scale, and nutritional program but no face-to-face care can achieve clinically significant weight loss in a large cohort. Design. Retrospective observational analysis. Setting. China from October 2016 to December 2017. Participants. Mobile application users with a minimum of 2 weights (baseline and ≥35 days). Intervention. A commercial (Weijian Technologies) weight loss program consisting of a dietary replacement, self-monitoring using a wireless home scale, and frequent guidance via mobile application. Main Outcome. Mean weight change around 42, 60, 90, and 120 days after program initiation with subgroup analysis by gender, age, and frequency of use. Results. 251,718 individuals, with a mean age of 37.3 years (SD: 9.86) (79% female), were included with a mean weight loss of 4.3 kg (CI: ±0.02) and a mean follow-up of 120 days (SD: 76.8 days). Mean weight loss at 42, 60, 90, and 120 d was 4.1 kg (CI: ±0.02), 4.9 kg (CI: ±0.02), 5.6 kg (CI: ±0.03), and 5.4 kg (CI: ±0.04), respectively. At 120 d, 62.7% of participants had lost at least 5% of their initial weight. Both genders and all usage frequency tertiles showed statistically significant weight loss from baseline at each interval (P<0.001), and this loss was greater in men than in women (120 d: 6.5 vs. 5.2 kg; P<0.001). The frequency of recording (categorized as high-, medium-, or low-frequency users) was associated with greater weight loss when comparing high, medium, and low tertile use groups at all time intervals investigated (e.g., 120 d: −8.6, −5.6, and −2.2 kg, respectively; P<0.001). Conclusions. People following a commercially available hybrid weight loss program using a mobile application, wireless scale, and nutritional program without face-to-face interaction on average achieved clinically significant short- and midterm weight loss. These results support the implementation of comparable technologies for weight control in a large population

Associations between single nucleotide polymorphisms in cellular viral receptors and attachment factor-related genes and humoral immunity to rubella vaccination.

Viral attachment and cell entry host factors are important for viral replication, pathogenesis, and the generation and sustenance of immune responses after infection and/or vaccination, and are plausible genetic regulators of vaccine-induced immunity.Using a tag-SNP approach in candidate gene study, we assessed the role of selected cell surface receptor genes, attachment factor-related genes, along with other immune genes in the genetic control of immune response variations after live rubella vaccination in two independent study cohorts.Our analysis revealed evidence for multiple associations between genetic variants in the PVR, PVRL2, CD209/DC-SIGN, RARB, MOG, IL6 and other immune function-related genes and rubella-specific neutralizing antibodies after vaccination (meta p-value <0.05).Our results indicate that multiple SNPs from genes involved in cell adhesion, viral attachment, and viral entry, as well as others in genes involved in signaling and/or immune response regulation, play a role in modulating humoral immune responses following live rubella vaccination

A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses

<div><p>Human antibody response to measles vaccine is highly variable in the population. Host genes contribute to inter-individual antibody response variation. The killer cell immunoglobulin-like receptors (KIR) are recognized to interact with HLA molecules and possibly influence humoral immune response to viral antigens. To expand on and improve our previous work with HLA genes, and to explore the genetic contribution of KIR genes to the inter-individual variability in measles vaccine-induced antibody responses, we performed a large population-based study in 2,506 healthy immunized subjects (ages 11 to 41 years) to identify HLA and KIR associations with measles vaccine-induced neutralizing antibodies. After correcting for the large number of statistical tests of allele effects on measles-specific neutralizing antibody titers, no statistically significant associations were found for either HLA or KIR loci. However, suggestive associations worthy of follow-up in other cohorts include B*57:01, DQB1*06:02, and DRB1*15:05 alleles. Specifically, the B*57:01 allele (1,040 mIU/mL; p = 0.0002) was suggestive of an association with lower measles antibody titer. In contrast, the DQB1*06:02 (1,349 mIU/mL; p = 0.0004) and DRB1*15:05 (2,547 mIU/mL; p = 0.0004) alleles were suggestive of an association with higher measles antibodies. Notably, the associations with KIR genotypes were strongly nonsignificant, suggesting that KIR loci in terms of copy number and haplotypes are not likely to play a major role in antibody response to measles vaccination. These findings refine our knowledge of the role of HLA and KIR alleles in measles vaccine-induced immunity.</p></div