2020
DOI: 10.1016/j.jaci.2019.09.035
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Shared genetic and experimental links between obesity-related traits and asthma subtypes in UK Biobank

Abstract: Key messagesd This large-scale cross-trait GWAS provides strong evidence for shared genetic components between obesityrelated metabolic traits and asthma subtypes.d The strongest positive genetic correlation was observed between obesity and later-onset asthma.d Mendelian randomization analysis provided strong evidence in support of BMI causally increasing the risk of asthma.

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Cited by 288 publications
(271 citation statements)
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“…In this review, we have summarized the current status of cross-trait genetics studies for the shared and distinct genetic effects between asthma subtypes and their shared genetics with coexistent diseases or traits. 12,[19][20][21][22][26][27][28][29]31 We have surveyed a broad range of major analytic methods at each phase of the genome-wide cross-trait analysis, namely, genetic correlation, cross-trait meta-analysis, Mendelian randomization, polygenic risk score, and functional analysis. We have also discussed scientific goals for each phase, as well as the advantages and limitations for these methods.…”
Section: Discussion and Future Directionsmentioning
confidence: 99%
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“…In this review, we have summarized the current status of cross-trait genetics studies for the shared and distinct genetic effects between asthma subtypes and their shared genetics with coexistent diseases or traits. 12,[19][20][21][22][26][27][28][29]31 We have surveyed a broad range of major analytic methods at each phase of the genome-wide cross-trait analysis, namely, genetic correlation, cross-trait meta-analysis, Mendelian randomization, polygenic risk score, and functional analysis. We have also discussed scientific goals for each phase, as well as the advantages and limitations for these methods.…”
Section: Discussion and Future Directionsmentioning
confidence: 99%
“…19,20 These fundamental studies largely depend on single-trait analysis, and they can be further extended by our recently implemented study design called genome-wide cross-trait analysis, which is broadly applicable to asthma and many other diseases and/or traits. The design has been successfully applied to the UK Biobank and GWAS consortia data sets and has determined the shared genetic architectures between asthma and allergic diseases, 22 obesity, 12 and mental health disorders, 21 which were reproducible in other studies. [26][27][28][29] A genome-wide cross-trait analysis features several analyses: genetic correlation, cross-trait meta-analysis, Mendelian randomization, polygenic risk score, and GWAS functional analysis.…”
Section: Genome-wide Cross-trait Analysis Study Designmentioning
confidence: 99%
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“…After this study was performed, new GWASs and functional annotation analysis have been published with new interesting asthma loci such as TNF receptor superfamily member 8 ( TNFRSF8 ) [ 143 ], and Collagen Type XVI Alpha 1 Chain ( COL16A1 ) [ 147 ], and more studies are to come. This is indeed very important since further functional activity experiments of candidate genes are still needed to understand the dynamic molecular events behind the pathogenesis of airway diseases.…”
Section: Therapeutic Implications and Future Prospectsmentioning
confidence: 99%
“…9 Interestingly, this individual was also noted to be obese (a common feature of ciliopathy syndromes); the CLUAP1 locus has been published as associated with BMI and type 2 diabetes in previous GWAS studies. [37][38][39][40]…”
Section: Cluap1mentioning
confidence: 99%