Human milk oligosaccharides are associated with maternal genetics and respiratory health of human milk-fed children

Amirthagowri Ambalavanan; Le Chang; Jihoon Choi; Yang Zhang; Sara A. Stickley; Zhi Y. Fang; Kozeta Miliku; Bianca Robertson; Chloe Yonemitsu; Stuart E. Turvey; Piushkumar J. Mandhane; Elinor Simons; Theo J. Moraes; Sonia S. Anand; Guillaume Paré; Janet E. Williams; Brenda M. Murdoch; Gloria E. Otoo; Samwel Mbugua; Elizabeth W. Kamau-Mbuthia; Egidioh W. Kamundia; Debela K. Gindola; Juan M. Rodriguez; Rossina G. Pareja; Daniel W. Sellen; Sophie E. Moore; Andrew M. Prentice; James A. Foster; Linda J. Kvist; Holly L. Neibergs; Mark A. McGuire; Michelle K. McGuire; Courtney L. Meehan; Malcolm R. Sears; Padmaja Subbarao; Meghan B. Azad; Lars Bode; Qingling Duan

doi:10.1038/s41467-024-51743-6

Human milk oligosaccharides are associated with maternal genetics and respiratory health of human milk-fed children

Amirthagowri Ambalavanan, Le Chang, Jihoon Choi, Yang Zhang, Sara A. Stickley, Zhi Y. Fang, Kozeta Miliku, Bianca Robertson, Chloe Yonemitsu, Stuart E. Turvey, Piushkumar J. Mandhane, Elinor Simons, Theo J. Moraes, Sonia S. Anand, Guillaume Paré, Janet E. Williams, Brenda M. Murdoch, Gloria E. Otoo, Samwel Mbugua, Elizabeth W. Kamau-MbuthiaEgidioh W. Kamundia, Debela K. Gindola, Juan M. Rodriguez, Rossina G. Pareja, Daniel W. Sellen, Sophie E. Moore, Andrew M. Prentice, James A. Foster, Linda J. Kvist, Holly L. Neibergs, Mark A. McGuire, Michelle K. McGuire, Courtney L. Meehan, Malcolm R. Sears, Padmaja Subbarao, Meghan B. Azad, Lars Bode, Qingling Duan

Department of Nutrition And Food Science

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Breastfeeding provides many health benefits, but its impact on respiratory health remains unclear. This study addresses the complex and dynamic nature of the mother-milk-infant triad by investigating maternal genomic factors regulating human milk oligosaccharides (HMOs), and their associations with respiratory health among human milk-fed infants. Nineteen HMOs are quantified from 980 mothers of the CHILD Cohort Study. Genome-wide association studies identify HMO-associated loci on chromosome 19p13.3 and 19q13.33 (lowest P = 2.4e–118), spanning several fucosyltransferase (FUT) genes. We identify novel associations on chromosome 3q27.3 for 6′-sialyllactose (P = 2.2e–9) in the sialyltransferase (ST6GAL1) gene. These, plus additional associations on chromosomes 7q21.32, 7q31.32 and 13q33.3, are replicated in the independent INSPIRE Cohort. Moreover, gene-environment interaction analyses suggest that fucosylated HMOs may modulate overall risk of recurrent wheeze among preschoolers with variable genetic risk scores (P < 0.01). Thus, we report novel genetic factors associated with HMOs, some of which may protect the respiratory health of children.

Original language	English
Article number	7735
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-51743-6
Publication status	Published - Dec 2024

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Ambalavanan, A., Chang, L., Choi, J., Zhang, Y., Stickley, S. A., Fang, Z. Y., Miliku, K., Robertson, B., Yonemitsu, C., Turvey, S. E., Mandhane, P. J., Simons, E., Moraes, T. J., Anand, S. S., Paré, G., Williams, J. E., Murdoch, B. M., Otoo, G. E., Mbugua, S., ... Duan, Q. (2024). Human milk oligosaccharides are associated with maternal genetics and respiratory health of human milk-fed children. Nature Communications, 15(1), Article 7735. https://doi.org/10.1038/s41467-024-51743-6

@article{e345584181574a8fb61bfb6dcd022872,

title = "Human milk oligosaccharides are associated with maternal genetics and respiratory health of human milk-fed children",

abstract = "Breastfeeding provides many health benefits, but its impact on respiratory health remains unclear. This study addresses the complex and dynamic nature of the mother-milk-infant triad by investigating maternal genomic factors regulating human milk oligosaccharides (HMOs), and their associations with respiratory health among human milk-fed infants. Nineteen HMOs are quantified from 980 mothers of the CHILD Cohort Study. Genome-wide association studies identify HMO-associated loci on chromosome 19p13.3 and 19q13.33 (lowest P = 2.4e–118), spanning several fucosyltransferase (FUT) genes. We identify novel associations on chromosome 3q27.3 for 6′-sialyllactose (P = 2.2e–9) in the sialyltransferase (ST6GAL1) gene. These, plus additional associations on chromosomes 7q21.32, 7q31.32 and 13q33.3, are replicated in the independent INSPIRE Cohort. Moreover, gene-environment interaction analyses suggest that fucosylated HMOs may modulate overall risk of recurrent wheeze among preschoolers with variable genetic risk scores (P < 0.01). Thus, we report novel genetic factors associated with HMOs, some of which may protect the respiratory health of children.",

author = "Amirthagowri Ambalavanan and Le Chang and Jihoon Choi and Yang Zhang and Stickley, {Sara A.} and Fang, {Zhi Y.} and Kozeta Miliku and Bianca Robertson and Chloe Yonemitsu and Turvey, {Stuart E.} and Mandhane, {Piushkumar J.} and Elinor Simons and Moraes, {Theo J.} and Anand, {Sonia S.} and Guillaume Par{\'e} and Williams, {Janet E.} and Murdoch, {Brenda M.} and Otoo, {Gloria E.} and Samwel Mbugua and Kamau-Mbuthia, {Elizabeth W.} and Kamundia, {Egidioh W.} and Gindola, {Debela K.} and Rodriguez, {Juan M.} and Pareja, {Rossina G.} and Sellen, {Daniel W.} and Moore, {Sophie E.} and Prentice, {Andrew M.} and Foster, {James A.} and Kvist, {Linda J.} and Neibergs, {Holly L.} and McGuire, {Mark A.} and McGuire, {Michelle K.} and Meehan, {Courtney L.} and Sears, {Malcolm R.} and Padmaja Subbarao and Azad, {Meghan B.} and Lars Bode and Qingling Duan",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1038/s41467-024-51743-6",

language = "English",

volume = "15",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

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Ambalavanan, A, Chang, L, Choi, J, Zhang, Y, Stickley, SA, Fang, ZY, Miliku, K, Robertson, B, Yonemitsu, C, Turvey, SE, Mandhane, PJ, Simons, E, Moraes, TJ, Anand, SS, Paré, G, Williams, JE, Murdoch, BM, Otoo, GE, Mbugua, S, Kamau-Mbuthia, EW, Kamundia, EW, Gindola, DK, Rodriguez, JM, Pareja, RG, Sellen, DW, Moore, SE, Prentice, AM, Foster, JA, Kvist, LJ, Neibergs, HL, McGuire, MA, McGuire, MK, Meehan, CL, Sears, MR, Subbarao, P, Azad, MB, Bode, L & Duan, Q 2024, 'Human milk oligosaccharides are associated with maternal genetics and respiratory health of human milk-fed children', Nature Communications, vol. 15, no. 1, 7735. https://doi.org/10.1038/s41467-024-51743-6

TY - JOUR

T1 - Human milk oligosaccharides are associated with maternal genetics and respiratory health of human milk-fed children

AU - Ambalavanan, Amirthagowri

AU - Chang, Le

AU - Choi, Jihoon

AU - Zhang, Yang

AU - Stickley, Sara A.

AU - Fang, Zhi Y.

AU - Miliku, Kozeta

AU - Robertson, Bianca

AU - Yonemitsu, Chloe

AU - Turvey, Stuart E.

AU - Mandhane, Piushkumar J.

AU - Simons, Elinor

AU - Moraes, Theo J.

AU - Anand, Sonia S.

AU - Paré, Guillaume

AU - Williams, Janet E.

AU - Murdoch, Brenda M.

AU - Otoo, Gloria E.

AU - Mbugua, Samwel

AU - Kamau-Mbuthia, Elizabeth W.

AU - Kamundia, Egidioh W.

AU - Gindola, Debela K.

AU - Rodriguez, Juan M.

AU - Pareja, Rossina G.

AU - Sellen, Daniel W.

AU - Moore, Sophie E.

AU - Prentice, Andrew M.

AU - Foster, James A.

AU - Kvist, Linda J.

AU - Neibergs, Holly L.

AU - McGuire, Mark A.

AU - McGuire, Michelle K.

AU - Meehan, Courtney L.

AU - Sears, Malcolm R.

AU - Subbarao, Padmaja

AU - Azad, Meghan B.

AU - Bode, Lars

AU - Duan, Qingling

PY - 2024/12

Y1 - 2024/12

N2 - Breastfeeding provides many health benefits, but its impact on respiratory health remains unclear. This study addresses the complex and dynamic nature of the mother-milk-infant triad by investigating maternal genomic factors regulating human milk oligosaccharides (HMOs), and their associations with respiratory health among human milk-fed infants. Nineteen HMOs are quantified from 980 mothers of the CHILD Cohort Study. Genome-wide association studies identify HMO-associated loci on chromosome 19p13.3 and 19q13.33 (lowest P = 2.4e–118), spanning several fucosyltransferase (FUT) genes. We identify novel associations on chromosome 3q27.3 for 6′-sialyllactose (P = 2.2e–9) in the sialyltransferase (ST6GAL1) gene. These, plus additional associations on chromosomes 7q21.32, 7q31.32 and 13q33.3, are replicated in the independent INSPIRE Cohort. Moreover, gene-environment interaction analyses suggest that fucosylated HMOs may modulate overall risk of recurrent wheeze among preschoolers with variable genetic risk scores (P < 0.01). Thus, we report novel genetic factors associated with HMOs, some of which may protect the respiratory health of children.

AB - Breastfeeding provides many health benefits, but its impact on respiratory health remains unclear. This study addresses the complex and dynamic nature of the mother-milk-infant triad by investigating maternal genomic factors regulating human milk oligosaccharides (HMOs), and their associations with respiratory health among human milk-fed infants. Nineteen HMOs are quantified from 980 mothers of the CHILD Cohort Study. Genome-wide association studies identify HMO-associated loci on chromosome 19p13.3 and 19q13.33 (lowest P = 2.4e–118), spanning several fucosyltransferase (FUT) genes. We identify novel associations on chromosome 3q27.3 for 6′-sialyllactose (P = 2.2e–9) in the sialyltransferase (ST6GAL1) gene. These, plus additional associations on chromosomes 7q21.32, 7q31.32 and 13q33.3, are replicated in the independent INSPIRE Cohort. Moreover, gene-environment interaction analyses suggest that fucosylated HMOs may modulate overall risk of recurrent wheeze among preschoolers with variable genetic risk scores (P < 0.01). Thus, we report novel genetic factors associated with HMOs, some of which may protect the respiratory health of children.

UR - http://www.scopus.com/inward/record.url?scp=85203265719&partnerID=8YFLogxK

U2 - 10.1038/s41467-024-51743-6

DO - 10.1038/s41467-024-51743-6

M3 - Article

AN - SCOPUS:85203265719

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 7735

ER -

Human milk oligosaccharides are associated with maternal genetics and respiratory health of human milk-fed children

Abstract

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