title: A genome-wide association study of n-3 and n-6 plasma fatty acids in a Singaporean Chinese population.
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.
authors.affiliation: Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Dorajoo
authors.affiliation: Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.
authors.forename: Ye
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 12, 1E Kent Ridge Road, Singapore, 119228, Singapore.|Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore.
authors.forename: Yi
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 12, 1E Kent Ridge Road, Singapore, 119228, Singapore.|Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore.
authors.forename: Tingjing
authors.initials: T
authors.lastname: Ke
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 12, 1E Kent Ridge Road, Singapore, 119228, Singapore.|Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore.|Unit of Epidemiology, Hebrew University-Hadassah Braun School of Public Health, POB 12272, 91120, Jerusalem, Israel.
authors.forename: Ayala
authors.initials: A
authors.lastname: Burger
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 12, 1E Kent Ridge Road, Singapore, 119228, Singapore.|Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore.
authors.forename: Xuling
authors.initials: X
authors.lastname: Chang
authors.affiliation: Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore.
authors.forename: Hui Qi
authors.initials: HQ
authors.lastname: Low
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Weihua
authors.initials: W
authors.lastname: Guan
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Rozenn N
authors.initials: RN
authors.lastname: Lemaitre
authors.affiliation: Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore.
authors.forename: Chiea-Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.|Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yuan
authors.affiliation: Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.|Duke-NUS Graduate Medical School Singapore, Singapore, Singapore.
authors.forename: Woon-Puay
authors.initials: WP
authors.lastname: Koh
authors.affiliation: Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.
authors.forename: Choon Nam
authors.initials: CN
authors.lastname: Ong
authors.affiliation: Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.|Duke-NUS Graduate Medical School Singapore, Singapore, Singapore.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: E Shyong
authors.initials: ES
authors.lastname: Tai
authors.affiliation: Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore.|Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.
authors.forename: Rob M
authors.initials: RM
authors.lastname: van Dam
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 12, 1E Kent Ridge Road, Singapore, 119228, Singapore. paehck@nus.edu.sg.|Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore. paehck@nus.edu.sg.
authors.forename: Chew-Kiat
authors.initials: CK
authors.lastname: Heng
authors.affiliation: Unit of Epidemiology, Hebrew University-Hadassah Braun School of Public Health, POB 12272, 91120, Jerusalem, Israel. yechielf@ekmd.huji.ac.il.
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Friedlander
keywords: Genome-wide association study; Polyunsaturated fatty acids; n-3 Fatty acids; n-6 Fatty acids