A case-only genome-wide association study for assessing gene-sex interaction in Allergic rhinitis

Publikation: Konferencebidrag uden forlag/tidsskriftPosterForskningpeer review

Resumé

Background: Allergic rhinitis (AR) is a complex disorder with important sex dependency in its prevalence. In this regard, genotype-by-sex interaction is one of the important phenomena in understanding the genetic basis of the disease. We aimed to apply a case-only genome-wide association study (GWAS) to assess the association of genotype-sex interaction. Methods: We genotyped 434 Danish subjects with AR, including 243 siblings and 191 unrelated individuals both male and female. SNP genotyping and imputation was done by using the Affymetrix Genome-wide Human SNP array 5.0 and IMPUT2 respectively. We conducted a single SNP analysis of GWAS, using generalized estimated equation (GEE) and specifying siblings as clusters. In addition, genebased test and biological pathway analysis were performed to detect functional genes and pathways implicated in AR. Results: We found 12 suggestive significant SNPs with p-value < 10−5 and also two enriched loci on chromosomes 5 and 12 from GWAS. Gene-based test showed the significant SNP rs4251459 with (β = 1.06, p-value = 1.28 × 10−5 ) is surrounded by three genes TWF1, PUS7L and IRAK4 on 12q12 locus. Another significant SNP rs566750 with (β = 0.67, p-value = 2.8 × 10−5) sits in C5orf66 gene on 5q31. Poster abstract 2 Discussion: Our study was able to detect a significant SNP rs4251459 mapping to IRAK4 gene on 12q12 locus which appeared to increase the risk of AR in females than males. This gene has previously been reported to have a sex dependent effect on AR. C5orf66 loci might also be an interesting candidate for AR, but its role warrants further validations. Additionally, pathway analysis from GSEA identified a pathway related to immune system which is biologically meaningful and supportive. In conclusion, our study revealed the gene-sex interaction in AR and displayed the usefulness of case-only design in GWAS.
OriginalsprogEngelsk
Publikationsdatoaug. 2017
StatusUdgivet - aug. 2017
BegivenhedThe 3rd Annual Danish Bioinformatics Conference, August 24-25, 2017, Odense, Denmark -
Varighed: 24. aug. 201725. aug. 2017
http://elixir-denmark.org/?page_id=2120

Konference

KonferenceThe 3rd Annual Danish Bioinformatics Conference, August 24-25, 2017, Odense, Denmark
Periode24/08/201725/08/2017
Internetadresse

Fingeraftryk

Genome-Wide Association Study
Single Nucleotide Polymorphism
Chromosomes, Human, Pair 12
Posters
Chromosomes, Human, Pair 5
Human Genome
Immune System

Citer dette

Mohammadnejad, A., Brasch-Andersen, C., Haagerup, A., Vestbo, J., Baumbach, J., & Tan, Q. (2017). A case-only genome-wide association study for assessing gene-sex interaction in Allergic rhinitis. Poster session præsenteret på The 3rd Annual Danish Bioinformatics Conference, August 24-25, 2017, Odense, Denmark, .
Mohammadnejad, Afsaneh ; Brasch-Andersen, Charlotte ; Haagerup, Annette ; Vestbo, Jørgen ; Baumbach, Jan ; Tan, Qihua. / A case-only genome-wide association study for assessing gene-sex interaction in Allergic rhinitis. Poster session præsenteret på The 3rd Annual Danish Bioinformatics Conference, August 24-25, 2017, Odense, Denmark, .
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abstract = "Background: Allergic rhinitis (AR) is a complex disorder with important sex dependency in its prevalence. In this regard, genotype-by-sex interaction is one of the important phenomena in understanding the genetic basis of the disease. We aimed to apply a case-only genome-wide association study (GWAS) to assess the association of genotype-sex interaction. Methods: We genotyped 434 Danish subjects with AR, including 243 siblings and 191 unrelated individuals both male and female. SNP genotyping and imputation was done by using the Affymetrix Genome-wide Human SNP array 5.0 and IMPUT2 respectively. We conducted a single SNP analysis of GWAS, using generalized estimated equation (GEE) and specifying siblings as clusters. In addition, genebased test and biological pathway analysis were performed to detect functional genes and pathways implicated in AR. Results: We found 12 suggestive significant SNPs with p-value < 10−5 and also two enriched loci on chromosomes 5 and 12 from GWAS. Gene-based test showed the significant SNP rs4251459 with (β = 1.06, p-value = 1.28 × 10−5 ) is surrounded by three genes TWF1, PUS7L and IRAK4 on 12q12 locus. Another significant SNP rs566750 with (β = 0.67, p-value = 2.8 × 10−5) sits in C5orf66 gene on 5q31. Poster abstract 2 Discussion: Our study was able to detect a significant SNP rs4251459 mapping to IRAK4 gene on 12q12 locus which appeared to increase the risk of AR in females than males. This gene has previously been reported to have a sex dependent effect on AR. C5orf66 loci might also be an interesting candidate for AR, but its role warrants further validations. Additionally, pathway analysis from GSEA identified a pathway related to immune system which is biologically meaningful and supportive. In conclusion, our study revealed the gene-sex interaction in AR and displayed the usefulness of case-only design in GWAS.",
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Mohammadnejad, A, Brasch-Andersen, C, Haagerup, A, Vestbo, J, Baumbach, J & Tan, Q 2017, 'A case-only genome-wide association study for assessing gene-sex interaction in Allergic rhinitis', The 3rd Annual Danish Bioinformatics Conference, August 24-25, 2017, Odense, Denmark, 24/08/2017 - 25/08/2017.

A case-only genome-wide association study for assessing gene-sex interaction in Allergic rhinitis. / Mohammadnejad, Afsaneh; Brasch-Andersen, Charlotte; Haagerup, Annette; Vestbo, Jørgen; Baumbach, Jan; Tan, Qihua.

2017. Poster session præsenteret på The 3rd Annual Danish Bioinformatics Conference, August 24-25, 2017, Odense, Denmark, .

Publikation: Konferencebidrag uden forlag/tidsskriftPosterForskningpeer review

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T1 - A case-only genome-wide association study for assessing gene-sex interaction in Allergic rhinitis

AU - Mohammadnejad, Afsaneh

AU - Brasch-Andersen, Charlotte

AU - Haagerup, Annette

AU - Vestbo, Jørgen

AU - Baumbach, Jan

AU - Tan, Qihua

PY - 2017/8

Y1 - 2017/8

N2 - Background: Allergic rhinitis (AR) is a complex disorder with important sex dependency in its prevalence. In this regard, genotype-by-sex interaction is one of the important phenomena in understanding the genetic basis of the disease. We aimed to apply a case-only genome-wide association study (GWAS) to assess the association of genotype-sex interaction. Methods: We genotyped 434 Danish subjects with AR, including 243 siblings and 191 unrelated individuals both male and female. SNP genotyping and imputation was done by using the Affymetrix Genome-wide Human SNP array 5.0 and IMPUT2 respectively. We conducted a single SNP analysis of GWAS, using generalized estimated equation (GEE) and specifying siblings as clusters. In addition, genebased test and biological pathway analysis were performed to detect functional genes and pathways implicated in AR. Results: We found 12 suggestive significant SNPs with p-value < 10−5 and also two enriched loci on chromosomes 5 and 12 from GWAS. Gene-based test showed the significant SNP rs4251459 with (β = 1.06, p-value = 1.28 × 10−5 ) is surrounded by three genes TWF1, PUS7L and IRAK4 on 12q12 locus. Another significant SNP rs566750 with (β = 0.67, p-value = 2.8 × 10−5) sits in C5orf66 gene on 5q31. Poster abstract 2 Discussion: Our study was able to detect a significant SNP rs4251459 mapping to IRAK4 gene on 12q12 locus which appeared to increase the risk of AR in females than males. This gene has previously been reported to have a sex dependent effect on AR. C5orf66 loci might also be an interesting candidate for AR, but its role warrants further validations. Additionally, pathway analysis from GSEA identified a pathway related to immune system which is biologically meaningful and supportive. In conclusion, our study revealed the gene-sex interaction in AR and displayed the usefulness of case-only design in GWAS.

AB - Background: Allergic rhinitis (AR) is a complex disorder with important sex dependency in its prevalence. In this regard, genotype-by-sex interaction is one of the important phenomena in understanding the genetic basis of the disease. We aimed to apply a case-only genome-wide association study (GWAS) to assess the association of genotype-sex interaction. Methods: We genotyped 434 Danish subjects with AR, including 243 siblings and 191 unrelated individuals both male and female. SNP genotyping and imputation was done by using the Affymetrix Genome-wide Human SNP array 5.0 and IMPUT2 respectively. We conducted a single SNP analysis of GWAS, using generalized estimated equation (GEE) and specifying siblings as clusters. In addition, genebased test and biological pathway analysis were performed to detect functional genes and pathways implicated in AR. Results: We found 12 suggestive significant SNPs with p-value < 10−5 and also two enriched loci on chromosomes 5 and 12 from GWAS. Gene-based test showed the significant SNP rs4251459 with (β = 1.06, p-value = 1.28 × 10−5 ) is surrounded by three genes TWF1, PUS7L and IRAK4 on 12q12 locus. Another significant SNP rs566750 with (β = 0.67, p-value = 2.8 × 10−5) sits in C5orf66 gene on 5q31. Poster abstract 2 Discussion: Our study was able to detect a significant SNP rs4251459 mapping to IRAK4 gene on 12q12 locus which appeared to increase the risk of AR in females than males. This gene has previously been reported to have a sex dependent effect on AR. C5orf66 loci might also be an interesting candidate for AR, but its role warrants further validations. Additionally, pathway analysis from GSEA identified a pathway related to immune system which is biologically meaningful and supportive. In conclusion, our study revealed the gene-sex interaction in AR and displayed the usefulness of case-only design in GWAS.

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M3 - Poster

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Mohammadnejad A, Brasch-Andersen C, Haagerup A, Vestbo J, Baumbach J, Tan Q. A case-only genome-wide association study for assessing gene-sex interaction in Allergic rhinitis. 2017. Poster session præsenteret på The 3rd Annual Danish Bioinformatics Conference, August 24-25, 2017, Odense, Denmark, .