Association of milk intake with hay fever, asthma, and lung function: a Mendelian randomization analysis

Tea Skaaby; Tuomas O. Kilpeläinen; Yuvaraj Mahendran; Lam Opal Huang; Hannah Sallis; Betina H. Thuesen; Line Lund Kårhus; Katja Biering Leth-Møller; Niels Grarup; Torben Hansen; Oluf Pedersen; Stephen Burgess; Marcus R. Munafò; Allan Linneberg

doi:10.1007/s10654-021-00826-5

Association of milk intake with hay fever, asthma, and lung function: a Mendelian randomization analysis

Tea Skaaby, Tuomas O. Kilpeläinen, Yuvaraj Mahendran, Lam Opal Huang, Hannah Sallis, Betina H. Thuesen, Line Lund Kårhus, Katja Biering Leth-Møller, Niels Grarup, Torben Hansen, Oluf Pedersen, Stephen Burgess, Marcus R. Munafò, Allan Linneberg

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Abstract

Background: Previous observational studies have indicated a protective effect of drinking milk on asthma and allergy. In Mendelian Randomization, one or more genetic variants are used as unbiased markers of exposure to examine causal effects. We examined the causal effect of milk intake on hay fever, asthma, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by using the lactase rs4988235 genotype associated with milk intake.

Methods: We performed a Mendelian Randomization study including 363,961 participants from the UK Biobank.

Results: Observational analyses showed that self-reported milk-drinkers vs. non-milk drinkers had an increased risk of hay fever: odds ratio (OR) = 1.36 (95% CI 1.32, 1.40, p < 0.001), asthma: OR = 1.33 (95% CI 1.38, 1.29, p < 0.001), yet a higher FEV1: β = 0.022 (SE = 0.004, p < 0.001) and FVC: β = 0.026 (SE = 0.005, p < 0.001). In contrast, genetically determined milk-drinking vs. not drinking milk was associated with a lower risk of hay fever: OR = 0.791 (95% CI 0.636, 0.982, p = 0.033), and asthma: OR = 0.587 (95% CI 0.442, 0.779, p = 0.001), and lower FEV1: β = − 0.154 (standard error, SE = 0.034, p < 0.001) liter, and FVC: β = − 0.223 (SE = 0.034, p < 0.001) liter in univariable MR analyses. These results were supported by multivariable Mendelian randomization analyses although not statistically significant.

Conclusions: As opposed to observational results, genetic association findings indicate that drinking milk has a protective effect on hay fever and asthma but may also have a negative effect on lung function. The results should be confirmed in other studies before any recommendations can be made.

Original language	English
Pages (from-to)	713-722
Number of pages	10
Journal	European Journal of Epidemiology
Volume	37
Issue number	7
Early online date	3 Jan 2022
DOIs	https://doi.org/10.1007/s10654-021-00826-5
Publication status	Published - 31 Jul 2022

Funding

Tea Skaaby was supported by grants from the Lundbeck Foundation (Grant number R165-2013-15410 and R219-2016-471), the Harboe Foundation (Grant number 16152), the A.P. Møller Foundation for the Advancement of Medical Science (Grant number 15-363), Aase and Einar Danielsen’s Foundation (Grant number 10-001490) and the Weimann’s grant. This research has been conducted using the UK Biobank Resource (Application number: 17765). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation ( www.metabol.ku.dk ).

Keywords

Allergic disease
Asthma
Hay fever
Lung function
Milk

ASJC Scopus subject areas

Epidemiology

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10.1007/s10654-021-00826-5

https://research-information.bris.ac.uk/en/publications/association-of-milk-intake-with-hay-fever-asthma-and-lung-functio

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Skaaby, T., Kilpeläinen, T. O., Mahendran, Y., Huang, L. O., Sallis, H., Thuesen, B. H., Kårhus, L. L., Leth-Møller, K. B., Grarup, N., Hansen, T., Pedersen, O., Burgess, S., Munafò, M. R., & Linneberg, A. (2022). Association of milk intake with hay fever, asthma, and lung function: a Mendelian randomization analysis. European Journal of Epidemiology, 37(7), 713-722. https://doi.org/10.1007/s10654-021-00826-5

Skaaby, T, Kilpeläinen, TO, Mahendran, Y, Huang, LO, Sallis, H, Thuesen, BH, Kårhus, LL, Leth-Møller, KB, Grarup, N, Hansen, T, Pedersen, O, Burgess, S, Munafò, MR & Linneberg, A 2022, 'Association of milk intake with hay fever, asthma, and lung function: a Mendelian randomization analysis', European Journal of Epidemiology, vol. 37, no. 7, pp. 713-722. https://doi.org/10.1007/s10654-021-00826-5

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title = "Association of milk intake with hay fever, asthma, and lung function: a Mendelian randomization analysis",

abstract = "Background: Previous observational studies have indicated a protective effect of drinking milk on asthma and allergy. In Mendelian Randomization, one or more genetic variants are used as unbiased markers of exposure to examine causal effects. We examined the causal effect of milk intake on hay fever, asthma, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by using the lactase rs4988235 genotype associated with milk intake. Methods: We performed a Mendelian Randomization study including 363,961 participants from the UK Biobank. Results: Observational analyses showed that self-reported milk-drinkers vs. non-milk drinkers had an increased risk of hay fever: odds ratio (OR) = 1.36 (95% CI 1.32, 1.40, p < 0.001), asthma: OR = 1.33 (95% CI 1.38, 1.29, p < 0.001), yet a higher FEV1: β = 0.022 (SE = 0.004, p < 0.001) and FVC: β = 0.026 (SE = 0.005, p < 0.001). In contrast, genetically determined milk-drinking vs. not drinking milk was associated with a lower risk of hay fever: OR = 0.791 (95% CI 0.636, 0.982, p = 0.033), and asthma: OR = 0.587 (95% CI 0.442, 0.779, p = 0.001), and lower FEV1: β = − 0.154 (standard error, SE = 0.034, p < 0.001) liter, and FVC: β = − 0.223 (SE = 0.034, p < 0.001) liter in univariable MR analyses. These results were supported by multivariable Mendelian randomization analyses although not statistically significant. Conclusions: As opposed to observational results, genetic association findings indicate that drinking milk has a protective effect on hay fever and asthma but may also have a negative effect on lung function. The results should be confirmed in other studies before any recommendations can be made.",

keywords = "Allergic disease, Asthma, Hay fever, Lung function, Milk",

author = "Tea Skaaby and Kilpel{\"a}inen, {Tuomas O.} and Yuvaraj Mahendran and Huang, {Lam Opal} and Hannah Sallis and Thuesen, {Betina H.} and K{\aa}rhus, {Line Lund} and Leth-M{\o}ller, {Katja Biering} and Niels Grarup and Torben Hansen and Oluf Pedersen and Stephen Burgess and Munaf{\`o}, {Marcus R.} and Allan Linneberg",

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doi = "10.1007/s10654-021-00826-5",

language = "English",

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TY - JOUR

T1 - Association of milk intake with hay fever, asthma, and lung function

T2 - a Mendelian randomization analysis

AU - Skaaby, Tea

AU - Kilpeläinen, Tuomas O.

AU - Mahendran, Yuvaraj

AU - Huang, Lam Opal

AU - Sallis, Hannah

AU - Thuesen, Betina H.

AU - Kårhus, Line Lund

AU - Leth-Møller, Katja Biering

AU - Grarup, Niels

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Burgess, Stephen

AU - Munafò, Marcus R.

AU - Linneberg, Allan

PY - 2022/7/31

Y1 - 2022/7/31

N2 - Background: Previous observational studies have indicated a protective effect of drinking milk on asthma and allergy. In Mendelian Randomization, one or more genetic variants are used as unbiased markers of exposure to examine causal effects. We examined the causal effect of milk intake on hay fever, asthma, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by using the lactase rs4988235 genotype associated with milk intake. Methods: We performed a Mendelian Randomization study including 363,961 participants from the UK Biobank. Results: Observational analyses showed that self-reported milk-drinkers vs. non-milk drinkers had an increased risk of hay fever: odds ratio (OR) = 1.36 (95% CI 1.32, 1.40, p < 0.001), asthma: OR = 1.33 (95% CI 1.38, 1.29, p < 0.001), yet a higher FEV1: β = 0.022 (SE = 0.004, p < 0.001) and FVC: β = 0.026 (SE = 0.005, p < 0.001). In contrast, genetically determined milk-drinking vs. not drinking milk was associated with a lower risk of hay fever: OR = 0.791 (95% CI 0.636, 0.982, p = 0.033), and asthma: OR = 0.587 (95% CI 0.442, 0.779, p = 0.001), and lower FEV1: β = − 0.154 (standard error, SE = 0.034, p < 0.001) liter, and FVC: β = − 0.223 (SE = 0.034, p < 0.001) liter in univariable MR analyses. These results were supported by multivariable Mendelian randomization analyses although not statistically significant. Conclusions: As opposed to observational results, genetic association findings indicate that drinking milk has a protective effect on hay fever and asthma but may also have a negative effect on lung function. The results should be confirmed in other studies before any recommendations can be made.

AB - Background: Previous observational studies have indicated a protective effect of drinking milk on asthma and allergy. In Mendelian Randomization, one or more genetic variants are used as unbiased markers of exposure to examine causal effects. We examined the causal effect of milk intake on hay fever, asthma, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by using the lactase rs4988235 genotype associated with milk intake. Methods: We performed a Mendelian Randomization study including 363,961 participants from the UK Biobank. Results: Observational analyses showed that self-reported milk-drinkers vs. non-milk drinkers had an increased risk of hay fever: odds ratio (OR) = 1.36 (95% CI 1.32, 1.40, p < 0.001), asthma: OR = 1.33 (95% CI 1.38, 1.29, p < 0.001), yet a higher FEV1: β = 0.022 (SE = 0.004, p < 0.001) and FVC: β = 0.026 (SE = 0.005, p < 0.001). In contrast, genetically determined milk-drinking vs. not drinking milk was associated with a lower risk of hay fever: OR = 0.791 (95% CI 0.636, 0.982, p = 0.033), and asthma: OR = 0.587 (95% CI 0.442, 0.779, p = 0.001), and lower FEV1: β = − 0.154 (standard error, SE = 0.034, p < 0.001) liter, and FVC: β = − 0.223 (SE = 0.034, p < 0.001) liter in univariable MR analyses. These results were supported by multivariable Mendelian randomization analyses although not statistically significant. Conclusions: As opposed to observational results, genetic association findings indicate that drinking milk has a protective effect on hay fever and asthma but may also have a negative effect on lung function. The results should be confirmed in other studies before any recommendations can be made.

KW - Allergic disease

KW - Asthma

KW - Hay fever

KW - Lung function

KW - Milk

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SN - 0393-2990

VL - 37

SP - 713

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JO - European Journal of Epidemiology

JF - European Journal of Epidemiology

IS - 7

ER -

Association of milk intake with hay fever, asthma, and lung function: a Mendelian randomization analysis

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