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

Genomics. 2021 Jul;113(4):1867-1875. doi: 10.1016/j.ygeno.2021.04.004. Epub 2021 Apr 6.

Authors

Janet E Williams¹, Michelle K McGuire², Courtney L Meehan³, Mark A McGuire¹, Sarah L Brooker¹, Elizabeth W Kamau-Mbuthia⁴, Egidioh W Kamundia⁴, Samwel Mbugua⁴, Sophie E Moore⁵, Andrew M Prentice⁶, Gloria E Otoo⁷, Juan M Rodríguez⁸, Rossina G Pareja⁹, James A Foster¹⁰, Daniel W Sellen¹¹, Debela G Kita¹², Holly L Neibergs¹³, Brenda M Murdoch¹⁴

Affiliations

¹ Department of Animal, Veterinary, and Food Sciences, University of Idaho, Moscow, ID 83844, USA.
² Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, ID 83844, USA.
³ Department of Anthropology, Washington State University, Pullman, WA 99164, USA.
⁴ Department of Human Nutrition, Egerton University, Nakuru, Kenya.
⁵ Department of Women and Children's Health, King's College London, London, United Kingdom; MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia.
⁶ MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia.
⁷ Department of Nutrition and Food Science, University of Ghana, Accra, Ghana.
⁸ Dpto. of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain.
⁹ Instituto de Investigación Nutricional, Lima, Peru.
¹⁰ Department of Biological Sciences and Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, ID, USA.
¹¹ Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
¹² Department of Anthropology, Hawassa University, Hawassa, Ethiopia.
¹³ Department of Animal Sciences, Washington State University, Pullman, WA, USA.
¹⁴ Department of Animal, Veterinary, and Food Sciences, University of Idaho, Moscow, ID 83844, USA. Electronic address: bmurdoch@uidaho.edu.

PMID: 33831438
DOI: 10.1016/j.ygeno.2021.04.004

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.

Keywords: FUT2; FUT3; GWAS; Human milk; Oligosaccharides.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Female
Genome-Wide Association Study*
Humans
Lactation
Milk, Human* / chemistry
Oligosaccharides* / chemistry

Substances

Oligosaccharides

Abstract

Publication types

MeSH terms

Substances

Grants and funding