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Genome-wide interaction study of gene-by-occupational exposure and effects on FEV1 levels  Kim de Jong, PhD, Judith M. Vonk, PhD, Wim Timens, PhD, Yohan.

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Presentation on theme: "Genome-wide interaction study of gene-by-occupational exposure and effects on FEV1 levels  Kim de Jong, PhD, Judith M. Vonk, PhD, Wim Timens, PhD, Yohan."— Presentation transcript:

1 Genome-wide interaction study of gene-by-occupational exposure and effects on FEV1 levels 
Kim de Jong, PhD, Judith M. Vonk, PhD, Wim Timens, PhD, Yohan Bossé, PhD, Don D. Sin, PhD, Ke Hao, PhD, Hans Kromhout, PhD, Roel Vermeulen, PhD, Dirkje S. Postma, PhD, H. Marike Boezen, PhD  Journal of Allergy and Clinical Immunology  Volume 136, Issue 6, Pages e14 (December 2015) DOI: /j.jaci Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Flow chart showing selection of SNPs. *One SNP reached genome-wide significance after meta-analysis. †Two SNPs reached genome-wide significance after meta-analysis. Journal of Allergy and Clinical Immunology  , e14DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Additive associations (for minor allele A1) between the SNP and the FEV1 level in subjects with no, low, and high exposure to biological dust. Journal of Allergy and Clinical Immunology  , e14DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Additive associations (for minor allele A1) between SNPs and FEV1 levels in subjects with no, low, and high exposure to mineral dust. SNPs presented are rs (A), rs (B), and rs (C). Journal of Allergy and Clinical Immunology  , e14DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Additive associations (for minor allele A1) between SNPs and FEV1 levels in subjects with no, low, and high exposure to gases and fumes. SNPs presented are rs (A), rs (B), and rs (C). Journal of Allergy and Clinical Immunology  , e14DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Gene expression levels stratified by genotype for cis-eQTL SNPs rs (A) and rs (B and C). SNP rs was associated with gene expression levels of both its left- and right-neighboring genes TMEM176A (Fig 5, B) and ABP1 (Fig 5, C), respectively. Journal of Allergy and Clinical Immunology  , e14DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig E1 Flow diagram showing the number of SNPs in each analysis.
Journal of Allergy and Clinical Immunology  , e14DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E2 QQ plots for the marginal association between SNPs and FEV1 levels in identification (A) and replication (B) samples. The analysis was adjusted for sex, age, height, and ever smoking (no/yes). Journal of Allergy and Clinical Immunology  , e14DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Fig E3 Regional association plots showing the 7 identified and replicated loci associated with FEV1 levels in interaction with biological dust (rs ), mineral dust (rs , rs473892, and rs ), and gases and fumes (rs159497, rs516732, and rs ) by using the online available software LocusZoom. Each SNP (sentinel SNP; purple diamond) ± 500 kb was plotted, with the y-axis showing the meta-analyzed (fixed-effects) −log P value, and the x-axis showing the chromosomal position (genome build hg18). Linkage disequilibrium with the sentinel SNP was plotted by using the 1000 Genomes Project population June 2010 CEU. Journal of Allergy and Clinical Immunology  , e14DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 Fig E3 Regional association plots showing the 7 identified and replicated loci associated with FEV1 levels in interaction with biological dust (rs ), mineral dust (rs , rs473892, and rs ), and gases and fumes (rs159497, rs516732, and rs ) by using the online available software LocusZoom. Each SNP (sentinel SNP; purple diamond) ± 500 kb was plotted, with the y-axis showing the meta-analyzed (fixed-effects) −log P value, and the x-axis showing the chromosomal position (genome build hg18). Linkage disequilibrium with the sentinel SNP was plotted by using the 1000 Genomes Project population June 2010 CEU. Journal of Allergy and Clinical Immunology  , e14DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

11 Fig E3 Regional association plots showing the 7 identified and replicated loci associated with FEV1 levels in interaction with biological dust (rs ), mineral dust (rs , rs473892, and rs ), and gases and fumes (rs159497, rs516732, and rs ) by using the online available software LocusZoom. Each SNP (sentinel SNP; purple diamond) ± 500 kb was plotted, with the y-axis showing the meta-analyzed (fixed-effects) −log P value, and the x-axis showing the chromosomal position (genome build hg18). Linkage disequilibrium with the sentinel SNP was plotted by using the 1000 Genomes Project population June 2010 CEU. Journal of Allergy and Clinical Immunology  , e14DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

12 Fig E3 Regional association plots showing the 7 identified and replicated loci associated with FEV1 levels in interaction with biological dust (rs ), mineral dust (rs , rs473892, and rs ), and gases and fumes (rs159497, rs516732, and rs ) by using the online available software LocusZoom. Each SNP (sentinel SNP; purple diamond) ± 500 kb was plotted, with the y-axis showing the meta-analyzed (fixed-effects) −log P value, and the x-axis showing the chromosomal position (genome build hg18). Linkage disequilibrium with the sentinel SNP was plotted by using the 1000 Genomes Project population June 2010 CEU. Journal of Allergy and Clinical Immunology  , e14DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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