Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes

Yong Song; Michelle J Schwager; Vibeke Backer; Jing Guo; Celeste Porsbjerg; Siew-Kim Khoo; Ingrid A Laing; Eric K Moses; Peter LeSouëf; Guicheng Brad Zhang

doi:10.1038/s41598-017-06791-y

Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes

Yong Song, Michelle J Schwager, Vibeke Backer, Jing Guo, Celeste Porsbjerg, Siew-Kim Khoo, Ingrid A Laing, Eric K Moses, Peter LeSouëf, Guicheng Brad Zhang

Department of Clinical Medicine

8 Citations (Scopus)

54 Downloads (Pure)

Abstract

The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit residing either in the westernized environment of Denmark or in the rural area of Greenland. Our results showed that lung function was associated with genetic variants in ORMDL3, with polymorphisms having a significant interaction with place of residence. LT-α SNP rs909253 and rs1041981 were significantly associated with bronchitis risk. LT-α SNP rs2844484 was related to dermatitis susceptibility and was significantly influenced by the place of residence. The observed gene-phenotype relationships were exclusively present in one population and absent in the other population. We conclude that the genotype-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases.

Original language	English
Article number	6342
Journal	Scientific Reports
Volume	7
Number of pages	10
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-017-06791-y
Publication status	Published - 1 Dec 2017

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title = "Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes",

abstract = "The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit residing either in the westernized environment of Denmark or in the rural area of Greenland. Our results showed that lung function was associated with genetic variants in ORMDL3, with polymorphisms having a significant interaction with place of residence. LT-α SNP rs909253 and rs1041981 were significantly associated with bronchitis risk. LT-α SNP rs2844484 was related to dermatitis susceptibility and was significantly influenced by the place of residence. The observed gene-phenotype relationships were exclusively present in one population and absent in the other population. We conclude that the genotype-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases.",

author = "Yong Song and Schwager, {Michelle J} and Vibeke Backer and Jing Guo and Celeste Porsbjerg and Siew-Kim Khoo and Laing, {Ingrid A} and Moses, {Eric K} and Peter LeSou{\"e}f and Zhang, {Guicheng Brad}",

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doi = "10.1038/s41598-017-06791-y",

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T1 - Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes

AU - Song, Yong

AU - Schwager, Michelle J

AU - Backer, Vibeke

AU - Guo, Jing

AU - Porsbjerg, Celeste

AU - Khoo, Siew-Kim

AU - Laing, Ingrid A

AU - Moses, Eric K

AU - LeSouëf, Peter

AU - Zhang, Guicheng Brad

PY - 2017/12/1

Y1 - 2017/12/1

N2 - The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit residing either in the westernized environment of Denmark or in the rural area of Greenland. Our results showed that lung function was associated with genetic variants in ORMDL3, with polymorphisms having a significant interaction with place of residence. LT-α SNP rs909253 and rs1041981 were significantly associated with bronchitis risk. LT-α SNP rs2844484 was related to dermatitis susceptibility and was significantly influenced by the place of residence. The observed gene-phenotype relationships were exclusively present in one population and absent in the other population. We conclude that the genotype-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases.

AB - The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit residing either in the westernized environment of Denmark or in the rural area of Greenland. Our results showed that lung function was associated with genetic variants in ORMDL3, with polymorphisms having a significant interaction with place of residence. LT-α SNP rs909253 and rs1041981 were significantly associated with bronchitis risk. LT-α SNP rs2844484 was related to dermatitis susceptibility and was significantly influenced by the place of residence. The observed gene-phenotype relationships were exclusively present in one population and absent in the other population. We conclude that the genotype-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases.

U2 - 10.1038/s41598-017-06791-y

DO - 10.1038/s41598-017-06791-y

M3 - Journal article

C2 - 28740106

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

M1 - 6342

ER -

Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes

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