Appendix A. Questionnaire for researchers involved in ecosystem services research.

Questionnaire for researchers involved in ecosystem services research

Six SNPs from two genomic regions significantly associated with celiac disease in Sweden.

<p>Five SNPs mapped to <i>PKIA</i> region and one SNP mapped <i>PFKFB3</i> region.</p

Novel associations with celiac disease or tissue transglutaminase autoantibody (tTGA) positivity (p<10⁻⁴).

<p>Novel associations with celiac disease or tissue transglutaminase autoantibody (tTGA) positivity (p<10⁻⁴).</p

Associations with risk of celiac disease in the Swedish population.

<p><b>A:</b> Manhattan plot of 133620 SNPs with MAF>0.01, displaying the <i>P</i>-values on the −log₁₀ scale for the SNPs associated with celiac disease in the Swedish TEDDY population. <b>B:</b> Regional association plots at the <i>PKIA</i> locus generated by LocusZoom, showing the significance of association and the recombination rate. Colors represent HapMap CEU linkage disequilibrium r² values with the most significantly associated SNP (rs117128341; shown in purple). <b>C:</b> Pairwise LD plot for five SNPs in the region of <i>PKIA</i>. The five most significant SNPs from this region are in high LD with each other.</p

Country-specific associations with risk of celiac disease.

<p>Kaplan-Meier plots of five SNPs mapped to the <i>PKIA</i> region and one SNP mapped to the <i>PFKFB3</i> region, in the Swedish TEDDY population (<b>A</b>) and in the other TEDDY countries (<b>B</b>). Kaplan-Meier plots clearly indicate country-specific differences. HRs and p-values are calculated using three possible genotypes and adjusted for family history of celiac disease, HLA-DR-DQ genotype, gender, <i>HLA-DPB1</i> and population stratification (ancestral heterogeneity).</p

SNPs in the previously reported celiac disease associated regions.

<p>Manhattan plot of <i>P</i>-values on the −log₁₀ scale for SNPs (±400kb) previously associated with celiac disease (<b>A</b>) and persistent tissue transglutaminase autoantibody (tTGA) positivity <b>(B</b>). HRs and p-values are calculated using three possible genotypes and adjusted for family history of celiac disease, HLA-DR-DQ genotype, gender, <i>HLA-DPB1</i>, population stratification (ancestral heterogeneity) and country of residence (as strata). The red dashed line represents <i>p</i> = 1x10⁻⁴. Kaplan-Meier plots of the three most significant SNPs associated with celiac disease (<b>C</b>) and tTGA (<b>D</b>) are plotted by dividing the subjects in two groups: (i) Major homozygous (black curves) and (ii) Heterozygous combined with minor homozygous (red curves).</p

Associations with risk of celiac disease and risk of persistent tissue transglutaminase autoantibody (tTGA) positivity.

<p>Manhattan plot of 133,620 SNPs with MAF>0.01, displaying the <i>P</i>-values on the −log₁₀ scale for SNP associations with celiac disease (<b>A</b>) and persistent tTGA positivity <b>(B</b>). HRs and p-values are calculated using three possible genotypes and adjusted for family history of celiac disease, HLA-DR-DQ genotype, gender, <i>HLA-DPB1</i>, population stratification (ancestral heterogeneity) and country of residence (as strata). The red dashed line represents <i>p</i> = 1x10⁻⁴, the red solid line represents Bonferroni correction threshold. Kaplan-Meier plots of selected SNPs associated with celiac disease (<b>C</b>) and persistent tTGA (<b>D</b>) are plotted by dividing the subjects in two groups: (i) Major homozygous (black curves) and (ii) Heterozygous combined with minor homozygous (red curves).</p

Associations with celiac disease or tissue transglutaminase autoantibody (tTGA) positivity (p<10⁻⁴), mapped to previously known regions.

<p>Associations with celiac disease or tissue transglutaminase autoantibody (tTGA) positivity (p<10⁻⁴), mapped to previously known regions.</p

Flow chart of study participants.

<p>The Environmental Determinants of Diabetes in the Young (TEDDY) is an international multicenter study that screened over 420,000 newborns from the general population in four different countries. The present study genotyped 195,806 SNPs on ImmunoChip in 6,010 TEDDY children to identify potential genetic factors responsible for the development of CD and country-specific differences in genetic predisposition. As shown in flow chart, a total of 6,010 subjects were included in the analysis of time-to-CD, and 5379 subjects were included in the analysis of time-to-tTGA.</p

A comprehensive evaluation of potential lung function associated genes in the SpiroMeta general population sample.

Rationale: Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium). Objectives: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample. Methods: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/−10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations. Results: The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3×10−5. The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81×10−5), CNTN5 (P = 4.37×10−4), and TRPV4 (P = 1.58×10−3). Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41×10−5), followed by PDE4D (P = 1.22×10−4). The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38×10−4), and ESR1 (P = 5.42×10−4) among ever-smokers. Conclusions: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population