Key genetic variants associated with variation of milk oligosaccharides from diverse human populations

Janet E. Williams; Michelle K. McGuire; Courtney L. Meehan; Mark A. McGuire; Sarah L. Brooker; Elizabeth W. Kamau-Mbuthia; Egidioh W. Kamundia; Samwel Mbugua; Sophie E. Moore; Andrew M. Prentice; Gloria E. Otoo; Juan M. Rodríguez; Rossina G. Pareja; James A. Foster; Daniel W. Sellen; Debela G. Kita; Holly L. Neibergs; Brenda M. Murdoch

doi:10.1016/j.ygeno.2021.04.004

Key genetic variants associated with variation of milk oligosaccharides from diverse human populations

Janet E. Williams, Michelle K. McGuire, Courtney L. Meehan, Mark A. McGuire, Sarah L. Brooker, Elizabeth W. Kamau-Mbuthia, Egidioh W. Kamundia, Samwel Mbugua, Sophie E. Moore, Andrew M. Prentice, Gloria E. Otoo, Juan M. Rodríguez, Rossina G. Pareja, James A. Foster, Daniel W. Sellen, Debela G. Kita, Holly L. Neibergs, Brenda M. Murdoch

Department of Nutrition And Food Science

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

29 Citations (Scopus)

Abstract

Human milk oligosaccharides (HMO), the third most abundant component of human milk, are thought to be important contributors to infant health. Studies have provided evidence that geography, stage of lactation, and Lewis and secretor blood groups are associated with HMO profile. However, little is known about how variation across the genome may influence HMO composition among women in various populations. In this study, we performed genome-wide association analyses of 395 women from 8 countries to identify genetic regions associated with 19 different HMO. Our data support FUT2 as the most significantly associated (P < 4.23⁻⁹ to P < 4.5⁻⁷⁰) gene with seven HMO and provide evidence of balancing selection for FUT2. Although polymorphisms in FUT3 were also associated with variation in lacto-N-fucopentaose II and difucosyllacto-N-tetrose, we found little evidence of selection on FUT3. To our knowledge, this is the first report of the use of genome-wide association analyses on HMO.

Original language	English
Pages (from-to)	1867-1875
Number of pages	9
Journal	Genomics
Volume	113
Issue number	4
DOIs	https://doi.org/10.1016/j.ygeno.2021.04.004
Publication status	Published - Jul 2021

Keywords

FUT2
FUT3
GWAS
Human milk
Oligosaccharides

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ygeno.2021.04.004

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Williams, J. E., McGuire, M. K., Meehan, C. L., McGuire, M. A., Brooker, S. L., Kamau-Mbuthia, E. W., Kamundia, E. W., Mbugua, S., Moore, S. E., Prentice, A. M., Otoo, G. E., Rodríguez, J. M., Pareja, R. G., Foster, J. A., Sellen, D. W., Kita, D. G., Neibergs, H. L., & Murdoch, B. M. (2021). Key genetic variants associated with variation of milk oligosaccharides from diverse human populations. Genomics, 113(4), 1867-1875. https://doi.org/10.1016/j.ygeno.2021.04.004

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title = "Key genetic variants associated with variation of milk oligosaccharides from diverse human populations",

abstract = "Human milk oligosaccharides (HMO), the third most abundant component of human milk, are thought to be important contributors to infant health. Studies have provided evidence that geography, stage of lactation, and Lewis and secretor blood groups are associated with HMO profile. However, little is known about how variation across the genome may influence HMO composition among women in various populations. In this study, we performed genome-wide association analyses of 395 women from 8 countries to identify genetic regions associated with 19 different HMO. Our data support FUT2 as the most significantly associated (P < 4.23−9 to P < 4.5−70) gene with seven HMO and provide evidence of balancing selection for FUT2. Although polymorphisms in FUT3 were also associated with variation in lacto-N-fucopentaose II and difucosyllacto-N-tetrose, we found little evidence of selection on FUT3. To our knowledge, this is the first report of the use of genome-wide association analyses on HMO.",

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author = "Williams, {Janet E.} and McGuire, {Michelle K.} and Meehan, {Courtney L.} and McGuire, {Mark A.} and Brooker, {Sarah L.} and Kamau-Mbuthia, {Elizabeth W.} and Kamundia, {Egidioh W.} and Samwel Mbugua and Moore, {Sophie E.} and Prentice, {Andrew M.} and Otoo, {Gloria E.} and Rodr{\'i}guez, {Juan M.} and Pareja, {Rossina G.} and Foster, {James A.} and Sellen, {Daniel W.} and Kita, {Debela G.} and Neibergs, {Holly L.} and Murdoch, {Brenda M.}",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

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doi = "10.1016/j.ygeno.2021.04.004",

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Williams, JE, McGuire, MK, Meehan, CL, McGuire, MA, Brooker, SL, Kamau-Mbuthia, EW, Kamundia, EW, Mbugua, S, Moore, SE, Prentice, AM, Otoo, GE, Rodríguez, JM, Pareja, RG, Foster, JA, Sellen, DW, Kita, DG, Neibergs, HL & Murdoch, BM 2021, 'Key genetic variants associated with variation of milk oligosaccharides from diverse human populations', Genomics, vol. 113, no. 4, pp. 1867-1875. https://doi.org/10.1016/j.ygeno.2021.04.004

TY - JOUR

T1 - Key genetic variants associated with variation of milk oligosaccharides from diverse human populations

AU - Williams, Janet E.

AU - McGuire, Michelle K.

AU - Meehan, Courtney L.

AU - McGuire, Mark A.

AU - Brooker, Sarah L.

AU - Kamau-Mbuthia, Elizabeth W.

AU - Kamundia, Egidioh W.

AU - Mbugua, Samwel

AU - Moore, Sophie E.

AU - Prentice, Andrew M.

AU - Otoo, Gloria E.

AU - Rodríguez, Juan M.

AU - Pareja, Rossina G.

AU - Foster, James A.

AU - Sellen, Daniel W.

AU - Kita, Debela G.

AU - Neibergs, Holly L.

AU - Murdoch, Brenda M.

PY - 2021/7

Y1 - 2021/7

N2 - Human milk oligosaccharides (HMO), the third most abundant component of human milk, are thought to be important contributors to infant health. Studies have provided evidence that geography, stage of lactation, and Lewis and secretor blood groups are associated with HMO profile. However, little is known about how variation across the genome may influence HMO composition among women in various populations. In this study, we performed genome-wide association analyses of 395 women from 8 countries to identify genetic regions associated with 19 different HMO. Our data support FUT2 as the most significantly associated (P < 4.23−9 to P < 4.5−70) gene with seven HMO and provide evidence of balancing selection for FUT2. Although polymorphisms in FUT3 were also associated with variation in lacto-N-fucopentaose II and difucosyllacto-N-tetrose, we found little evidence of selection on FUT3. To our knowledge, this is the first report of the use of genome-wide association analyses on HMO.

AB - Human milk oligosaccharides (HMO), the third most abundant component of human milk, are thought to be important contributors to infant health. Studies have provided evidence that geography, stage of lactation, and Lewis and secretor blood groups are associated with HMO profile. However, little is known about how variation across the genome may influence HMO composition among women in various populations. In this study, we performed genome-wide association analyses of 395 women from 8 countries to identify genetic regions associated with 19 different HMO. Our data support FUT2 as the most significantly associated (P < 4.23−9 to P < 4.5−70) gene with seven HMO and provide evidence of balancing selection for FUT2. Although polymorphisms in FUT3 were also associated with variation in lacto-N-fucopentaose II and difucosyllacto-N-tetrose, we found little evidence of selection on FUT3. To our knowledge, this is the first report of the use of genome-wide association analyses on HMO.

KW - FUT2

KW - FUT3

KW - GWAS

KW - Human milk

KW - Oligosaccharides

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U2 - 10.1016/j.ygeno.2021.04.004

DO - 10.1016/j.ygeno.2021.04.004

M3 - Article

C2 - 33831438

AN - SCOPUS:85105260821

SN - 0888-7543

VL - 113

SP - 1867

EP - 1875

JO - Genomics

JF - Genomics

IS - 4

ER -

Key genetic variants associated with variation of milk oligosaccharides from diverse human populations

Abstract

Keywords

UN SDGs

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