Maternal age-related DNA methylation changes in newborns (NFCS and MoBa) and adults (Sister Study) per 20 years.

<p>Methylation at each CpG (β-value) was tested for association with maternal age and the β coefficients from the regression analysis were converted into the percent difference in methylation per 20 years (maternal age). The covariates included in Model1 differed slightly across the NFCS, MoBa, and the Sister Study analyses (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156361#pone.0156361.s013" target="_blank">S1 Text</a>).</p

Epigenome-wide association results of maternal age in NFCS newborns.

<p>Volcano plot showing the relationship between the effect magnitude (coefficient) and strength of association (p-value) for Model1. The red horizontal line denotes the strict threshold for epigenome-wide significance based on a conservative Bonferroni correction for 465525 tests (p < 1.07x10^-7). The four CpGs that are circled in purple are near the second exon of the gene, <i>KLHL35</i>.</p

Boxplots showing the distribution of % CpG methylation after normalization and batch correction using COMBAT by IUS exposure for A) <i>C11orf52</i> (cg05697249), B) <i>XPNPEP1</i> (cg09352789), C) <i>FRMD4A</i> (cg25464840), and D) <i>PPEF2</i> (cg14724265) in 526 Asthma BRIDGE samples.

<p>Boxplots showing the distribution of % CpG methylation after normalization and batch correction using COMBAT by IUS exposure for A) <i>C11orf52</i> (cg05697249), B) <i>XPNPEP1</i> (cg09352789), C) <i>FRMD4A</i> (cg25464840), and D) <i>PPEF2</i> (cg14724265) in 526 Asthma BRIDGE samples.</p

CpG Loci significantly associated with IUS exposure in CAMP asthmatics (N = 527).

<p>CpG Loci significantly associated with IUS exposure in CAMP asthmatics (N = 527).</p

Replication results from beta regression and linear regression models in Asthma BRIDGE and MoBa for the 19 CpG loci identified in CAMP.

<p>Replication results from beta regression and linear regression models in Asthma BRIDGE and MoBa for the 19 CpG loci identified in CAMP.</p

Association of the most statistically significant SNPs with the rate of change in FEV₁ (mL/year) in the meta-analysis of the five cohort studies with ≥3 FEV₁ measurements per participant (n = 10,476).

<p><i>Definition of abbreviations</i>: Chr  =  chromosome; SE  =  standard error; SNP  =  single-nucleotide polymorphism.</p><p>^*Data reported are the meta-analysis results of the SNP-by-time interaction term from the GWAS mixed effects model. A positive β-coefficient indicates an attenuation of FEV₁ decline and a negative β-coefficient an acceleration of FEV₁ decline.</p

Association of the chromosome 15 locus with the rate of change in FEV₁ in the meta-analysis of 14 cohort studies.

<p><b>A</b>) Regional association plot, where the X-axis is Megabase (Mb) position and Y-axes are the negative log of the <i>P</i> value on the left and recombination rate on the right. The sentinel SNP is colored in purple and linkage disequilibrium to the sentinel SNP is depicted by degree of color according to the legend. <b>B</b>) Forest plot for rs4077833, where the size of the square for each study represents its contributing weight to the meta-analysis.</p

Baseline characteristics of cohort studies included in the meta-analysis^*.

<p><i>Definition of abbreviations</i>: ARIC  =  Atherosclerosis Risk in Communities; B58C  =  British 1958 Birth Cohort; BHS  =  Busselton Health Study; CARDIA  =  Coronary Artery Risk Development in Young Adults; CHS  =  Cardiovascular Health Study  =  FHS, Framingham Heart Study; Health ABC  =  Health, Aging, and Body Composition; KORA  =  Cooperative Health Research in the Region of Augsburg; LBC1921  =  Lothian Birth Cohort 1921; LBC1936  =  Lothian Birth Cohort 1936; PIVUS  =  Prospective Investigation of the Vasculature in Uppsala Seniors; RS  =  Rotterdam Study; SAPALDIA  =  Swiss Study on Air Pollution and Lung Diseases in Adults; SD  =  standard deviation; SHIP  =  Study of Health in Pomerania.</p><p>^*Data are presented as mean (SD) unless otherwise indicated; total no. participants  =  27,249, total no. FEV₁ measurements  =  62,130.</p>†<p>Pack-years are calculated among current and former smokers at study baseline.</p

Genome-wide significant SNPs from the joint meta-analysis (JMA) of SNP and SNP-by-smoking (ever-smoking or pack-years) interaction in relation to pulmonary function.

<p>After removing SNPs with known associations with FEV₁/FVC or FEV₁, three novel loci with genome-wide significant SNPs (standard threshold of <i>P</i>&lt;5×10⁻⁸) remained from the JMA testing in the current study. The most significant SNP from each locus is shown.</p><p>FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; JMA, joint meta-analysis; SE, standard error ; SNP, single nucleotide polymorphism.</p>1<p>Weighted average coded allele frequency across the 19 studies. The coded allele refers to the effect allele.</p>2<p>β_SNP, per allele change in the FEV₁/FVC standardized residual due to the SNP main association.</p>3<p>β_INT, per allele change in the FEV₁/FVC standardized residual due to the interaction between SNP and smoking.</p

Association of the most statistically significant SNPs with the rate of change in FEV₁ (mL/year) in the meta-analysis of 14 cohort studies (n = 27,249)^*.

<p><i>Definition of abbreviations</i>: Chr  =  chromosome; SE  =  standard error; SNP  =  single-nucleotide polymorphism.</p><p>^*Data reported are the meta-analysis results of the SNP-by-time interaction term from the GWAS mixed effects model. A positive β-coefficient indicates an attenuation of FEV₁ decline and a negative β-coefficient an acceleration of FEV₁ decline.</p