Association between nocturia and presence of sleep-disordered breathing based upon different apnea-hypopnea index (AHI) thresholds are shown as odds ratio (<i>symbol</i>) and 95% confidence intervals (<i>y-error bars</i>).

<p>Odds ratios and respective confidence intervals that were adjusted for confounders (<i>left panel</i>) and unadjusted for confounders (<i>right panel</i>) are shown. The x-axis of each panel represents nocturia expressed as a dichotomous categorical variable (nocturia present or absent) by progressively increasing the threshold level of collapse from ‘rarely’ to ‘always’ to yield four different dichotomous variables for nocturia. The cluster of three symbols with corresponding error bars for each definition of nocturia correspond to variable AHI thresholds for nocturia from left-to-right (>15, >10 and >5 per hour, respectively). For nocturia defined as greater than rarely (<i>closed triangle</i>) only one adjusted odds ratio is shown (<i>left panel</i>) because multivariate regression was performed only if univariate regression was significant at P<0.05 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030969#s2" target="_blank">methods</a>).</p

Proportions and numbers of patients with reported frequency of nocturia.

<p>Participants were queried as to how often in the prior year, did they awaken to go to the bathroom: never, rarely (1/month or less), sometimes (2–4/month), often (5–15/month), and almost always (16–30/month).</p

Participant Characteristics.

<p>Kg/m² = kilogram/meter²; FEV1 = Forced expiratory volume; hr = hour; proportions compared by Chi square; Mann-Whitney test for non-parametrics (presented as median and interquartile range); unpaired t-test for parametric variables (presented as mean ± SD); AHI = apnea-hypopnea index.</p

Variables Associated With Presence Of Nocturia.^†

<p>AHI = respiratory disturbance index; BMI = body mass index; FEV₁ = forced expiratory volume in one second; CI = confidence interval;</p><p>*dichotomous variables;</p>†<p>continuous variable.</p>§<p>Multiple regression that adjusts for age, BMI, alcohol, diuretics, FEV₁, α-blocker, coffee and soda.</p

Adjusted And Unadjusted Odds Ratios Of Associations with Hypertension.

<p>BMI = body mass index; AHI = apnea hypopnea index; diabetes = diabetes mellitus; B = estimated coefficient; SE = standard error; CI = confidence intervals.</p><p>*African-Americans compared to all other races combined;</p>†<p>per cigarette pack year;</p>‡<p>per inch neck circumference;</p>§<p>compared to absence of diabetes mellitus;</p>∥<p>per unit apnea-hypopnea index (>4% desaturation for hypopnea; <i>continuous variable</i>);</p><p>**compared to no diuretic;</p>††<p>per unit change in ratio.</p>§§<p>WASO = time awake after sleep onset;</p>∥∥<p>Arousals = arousal index expressed as arousals per hour of sleep;</p>‡‡<p>Nocturia was defined as ‘often’ (occurring at least 5 times per month).</p><p>***P<0.05;</p>†††<p>P<0.0001.</p

Adjusted Odds Ratios Of Associations Between Nocturia and Prevalent Cardiovascular Morbidity.

<p>*Adjusted for age, gender, race, smoking, diabetes mellitus, hypertension, systolic blood pressure, body mass index, total cholesterol, and high density lipoprotein levels.</p>†<p>Adjusted for sleep-disordered breathing (SDB; measured as apnea-hypopnea index) in addition to other confounders listed^*. Nocturia was defined as ‘often’ (occurring at least 5 times per month).</p>§<p>WASO = time awake after sleep onset;</p>∥<p>arousal index expressed as arousals per hour of sleep;</p>‡<p>P<0.05.</p

Mean topological overlap for proteins associated to asthma, eczema and rhinitis.

<p>(A) Blue dots indicate the observed mean topological overlap (TO) for proteins common to asthma and eczema, asthma and rhinitis, eczema and rhinitis, and common to all three. Orange scatter boxplots indicate random expectation. (B) Blue dots indicate the observed mean TO for proteins common to the combinations of diseases shown in the previous figure. Orange scatter boxplots indicate observed TO values for pairs/trios of immune system diseases. (C) Blue dots indicate the observed mean TO between proteins unique to asthma and unique to eczema, unique to asthma and unique to rhinitis, unique to eczema and unique to rhinitis, and unique to each disease. Orange scatter boxplots indicate random expectation. (D) Blue dots indicate the observed mean TO for proteins unique to the combinations of diseases shown in the previous figure. Orange scatter boxplots indicate observed TO values for pairs/trios of immune system diseases. One asterisk: observed results are significantly larger than random expectation (<i>P</i> < 0.05). Two asterisks: observed results are significantly larger than random expectation (<i>P</i> < 0.01).</p

Statistical association between predicted multimorbidity-associated proteins and literature predictions.

<p>Literature predictions were automatically extracted from PubMed abstracts using the Génie data mining tool. Statistical association was calculated by means of a Fisher's Exact Test. Confidence intervals are shown in parentheses.</p

Potential disease-associated proteins predicted for asthma, eczema and rhinitis.

<p>NetZcore prediction scores are shown as <i>z</i>-scores. Proteins are ranked according to their average <i>z</i>-score for all diseases. Empty cell: the protein was not predicted to be associated with the disease with <i>z</i>-score > 2.31 (corresponding to <i>P</i> < 0.01). <i>Exp</i>: the protein is experimentally known to be associated to the disease. This table only shows the 30 top-scoring proteins that were found to be associated to more than one disease. The complete list is available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179125#pone.0179125.s023" target="_blank">S12 Table</a>.</p

Functional Interaction Networks of asthma, eczema and rhinitis.

<p>Fraction of the Functional Interaction Networks comprising the proteins associated to asthma, eczema, rhinitis and all proteins connected to them (i.e. their direct neighbors in the network). A node represents a protein. A link between two nodes represents a functional connection between them. Isolated nodes represent proteins not directly connected neither to any other disease-associated protein nor to any of its direct neighbors. (A) Large red nodes represent asthma-associated proteins. Red links represent functional connections of these proteins. (B) Large yellow nodes represent eczema-associated proteins. Yellow links represent functional connections of these proteins. (C) Large blue nodes represent rhinitis-associated proteins. Blue links represent functional connections of these proteins.</p