A genome-wide association study of n-3 and n-6 plasma fatty acids in a Singaporean Chinese population

Rajkumar Dorajoo; Ye Sun; Yi Han; Tingjing Ke; Ayala Burger; Xuling Chang; Hui Qi Low; Weihua Guan; Rozenn N. Lemaitre; Chiea Chuen Khor; Jian Min Yuan; Woon Puay Koh; Choon Nam Ong; E. Shyong Tai; Jianjun Liu; Rob M. van Dam; Chew Kiat Heng; Yechiel Friedlander

doi:10.1007/s12263-015-0502-2

A genome-wide association study of n-3 and n-6 plasma fatty acids in a Singaporean Chinese population

Rajkumar Dorajoo, Ye Sun, Yi Han, Tingjing Ke, Ayala Burger, Xuling Chang, Hui Qi Low, Weihua Guan, Rozenn N. Lemaitre, Chiea Chuen Khor, Jian Min Yuan, Woon Puay Koh, Choon Nam Ong, E. Shyong Tai, Jianjun Liu, Rob M. van Dam, Chew Kiat Heng, Yechiel Friedlander

Biostatistics

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

46 Scopus citations

Abstract

Polyunsaturated fatty acids (PUFAs) have a major impact on human health. Recent genome-wide association studies (GWAS) have identified several genetic loci that are associated with plasma levels of n-3 and n-6 PUFAs in primarily subjects of European ancestry. However, the relevance of these findings has not been evaluated extensively in other ethnic groups. The primary aim of this study was to evaluate for genetic loci associated with n-3 and n-6 PUFAs and to validate the role of recently identified index loci using data from a Singaporean Chinese population. Using a GWAS approach, we evaluated associations with plasma concentrations of three n-3 PUFAs [alphalinolenic acid (ALA), eicosapentaenoic acid and docosahexaenoic acid], four n-6 PUFAs [linoleic acid (LA), gammalinolenic acid, dihomogammalinolenic acid (DGLA) and arachidonic acid], and estimates of delta-5 desaturase and delta-6 desaturase activities among the participants (N = 1361) of the Singaporean Chinese Health Study. Our results reveal robust genome-wide associations (p value <5 × 10⁻⁸) with ALA, all four n-6 PUFAs, and delta-6 desaturase activity at the FADS1/FADS2 locus. We further replicated the associations between common index variants at the NTAN1/PDXDC1 locus and n-6 PUFAs LA and DGLA, and between the JMJD1C locus and n-6 PUFA LA (p value between 0.0490 and 9.88 × 10⁻⁴). These associations were independent of dietary intake of PUFAs. In aggregate, we show that genetic loci that influence plasma concentrations of n-3 and n-6 PUFAs are shared across different ethnic groups.

Original language	English (US)
Article number	53
Pages (from-to)	1-11
Number of pages	11
Journal	Genes and Nutrition
Volume	10
Issue number	6
DOIs	https://doi.org/10.1007/s12263-015-0502-2
State	Published - Nov 1 2015

Bibliographical note

Funding Information:
Acknowledgments We thank Siew-Hong Low of the National University of Singapore for supervising the fieldwork and Renwei Wang for the maintenance of the database in the Singapore Chinese Health Study. We also thank the Ministry of Health in Singapore for assistance with the identification of fatal and non-fatal myocardial infarction cases via database linkages. Finally, we acknowledge the founding Principal Investigator of the Singapore Chinese Health Study, Mimi C. Yu. The Singapore Chinese Health Study was supported by the National Institutes of Health, USA (RO1 CA144034 and UM1 CA182876), the nested case–control study of myocardial infarction by the Singapore National Medical Research Council (NMRC 1270/2010) and genotyping by the HUJ-CREATE Programme of the National Research Foundation, Singapore (Project Number 370062002).

Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.

Keywords

Genome-wide association study
Polyunsaturated fatty acids
n-3 Fatty acids
n-6 Fatty acids

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Dorajoo, R., Sun, Y., Han, Y., Ke, T., Burger, A., Chang, X., Low, H. Q., Guan, W., Lemaitre, R. N., Khor, C. C., Yuan, J. M., Koh, W. P., Ong, C. N., Tai, E. S., Liu, J., van Dam, R. M., Heng, C. K., & Friedlander, Y. (2015). A genome-wide association study of n-3 and n-6 plasma fatty acids in a Singaporean Chinese population. Genes and Nutrition, 10(6), 1-11. Article 53. https://doi.org/10.1007/s12263-015-0502-2

Dorajoo, R, Sun, Y, Han, Y, Ke, T, Burger, A, Chang, X, Low, HQ, Guan, W, Lemaitre, RN, Khor, CC, Yuan, JM, Koh, WP, Ong, CN, Tai, ES, Liu, J, van Dam, RM, Heng, CK & Friedlander, Y 2015, 'A genome-wide association study of n-3 and n-6 plasma fatty acids in a Singaporean Chinese population', Genes and Nutrition, vol. 10, no. 6, 53, pp. 1-11. https://doi.org/10.1007/s12263-015-0502-2

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abstract = "Polyunsaturated fatty acids (PUFAs) have a major impact on human health. Recent genome-wide association studies (GWAS) have identified several genetic loci that are associated with plasma levels of n-3 and n-6 PUFAs in primarily subjects of European ancestry. However, the relevance of these findings has not been evaluated extensively in other ethnic groups. The primary aim of this study was to evaluate for genetic loci associated with n-3 and n-6 PUFAs and to validate the role of recently identified index loci using data from a Singaporean Chinese population. Using a GWAS approach, we evaluated associations with plasma concentrations of three n-3 PUFAs [alphalinolenic acid (ALA), eicosapentaenoic acid and docosahexaenoic acid], four n-6 PUFAs [linoleic acid (LA), gammalinolenic acid, dihomogammalinolenic acid (DGLA) and arachidonic acid], and estimates of delta-5 desaturase and delta-6 desaturase activities among the participants (N = 1361) of the Singaporean Chinese Health Study. Our results reveal robust genome-wide associations (p value <5 × 10−8) with ALA, all four n-6 PUFAs, and delta-6 desaturase activity at the FADS1/FADS2 locus. We further replicated the associations between common index variants at the NTAN1/PDXDC1 locus and n-6 PUFAs LA and DGLA, and between the JMJD1C locus and n-6 PUFA LA (p value between 0.0490 and 9.88 × 10−4). These associations were independent of dietary intake of PUFAs. In aggregate, we show that genetic loci that influence plasma concentrations of n-3 and n-6 PUFAs are shared across different ethnic groups.",

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author = "Rajkumar Dorajoo and Ye Sun and Yi Han and Tingjing Ke and Ayala Burger and Xuling Chang and Low, {Hui Qi} and Weihua Guan and Lemaitre, {Rozenn N.} and Khor, {Chiea Chuen} and Yuan, {Jian Min} and Koh, {Woon Puay} and Ong, {Choon Nam} and Tai, {E. Shyong} and Jianjun Liu and {van Dam}, {Rob M.} and Heng, {Chew Kiat} and Yechiel Friedlander",

note = "Funding Information: Acknowledgments We thank Siew-Hong Low of the National University of Singapore for supervising the fieldwork and Renwei Wang for the maintenance of the database in the Singapore Chinese Health Study. We also thank the Ministry of Health in Singapore for assistance with the identification of fatal and non-fatal myocardial infarction cases via database linkages. Finally, we acknowledge the founding Principal Investigator of the Singapore Chinese Health Study, Mimi C. Yu. The Singapore Chinese Health Study was supported by the National Institutes of Health, USA (RO1 CA144034 and UM1 CA182876), the nested case–control study of myocardial infarction by the Singapore National Medical Research Council (NMRC 1270/2010) and genotyping by the HUJ-CREATE Programme of the National Research Foundation, Singapore (Project Number 370062002). Publisher Copyright: {\textcopyright} 2015, Springer-Verlag Berlin Heidelberg.",

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AU - Han, Yi

AU - Ke, Tingjing

AU - Burger, Ayala

AU - Chang, Xuling

AU - Low, Hui Qi

AU - Guan, Weihua

AU - Lemaitre, Rozenn N.

AU - Khor, Chiea Chuen

AU - Yuan, Jian Min

AU - Koh, Woon Puay

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AU - Tai, E. Shyong

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AU - van Dam, Rob M.

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AU - Friedlander, Yechiel

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A genome-wide association study of n-3 and n-6 plasma fatty acids in a Singaporean Chinese population

Abstract

Bibliographical note

Keywords

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