Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in chinese and european-ancestry populations

Yao Hu; Huaixing Li; Ling Lu; Ani Manichaikul; Jingwen Zhu; I. Yii Der Chen; Liang Sun; Shuang Liang; David S. Siscovick; Lyn M. Steffen; Michael Y. Tsai; Stephen S. Rich; Rozenn N. Lemaitre; Xu Lin

doi:10.1093/hmg/ddw002

Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in chinese and european-ancestry populations

Yao Hu, Huaixing Li, Ling Lu, Ani Manichaikul, Jingwen Zhu, I. Yii Der Chen, Liang Sun, Shuang Liang, David S. Siscovick, Lyn M. Steffen, Michael Y. Tsai, Stephen S. Rich, Rozenn N. Lemaitre, Xu Lin

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

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Abstract

Epidemiological studies suggest that levels of n-3 and n-6 long-chain polyunsaturated fatty acids are associated with risk of cardio-metabolic outcomes across different ethnic groups. Recent genome-wide association studies in populations of European ancestry have identified several loci associated with plasma and/or erythrocyte polyunsaturated fatty acids. To identify additional novel loci, we carried out a genome-wide association study in two population-based cohorts consisting of 3521 Chinese participants, followed by a trans-ethnic meta-analysis with meta-analysis results from 8962 participants of European ancestry. Four novel loci (MYB, AGPAT4, DGAT2 and PPT2) reached genome-wide significance in the trans-ethnic meta-analysis (log10(Bayes Factor) ≥ 6). Of them, associations of MYB and AGPAT4 with docosatetraenoic acid (log10(Bayes Factor) = 11.5 and 8.69, respectively) also reached genome-wide significance in the Chinese-specific genome-wide association analyses (P = 4.15 × 10^-14 and 4.30 × 10^-12, respectively), while associations of DGAT2 with gamma-linolenic acid (log10(Bayes Factor) = 6.16) and of PPT2 with docosapentaenoic acid (log10(Bayes Factor) = 6.24) were nominally significant in both Chinese- and European-specific genome-wide association analyses (P ≤ 0.003). We also confirmed previously reported loci including FADS1, NTAN1, NRBF2, ELOVL2 and GCKR. Different effect sizes in FADS1 and independent association signals in ELOVL2 were observed. These results provide novel insight into the genetic background of polyunsaturated fatty acids and their differences between Chinese and European populations.

Original language	English
Pages (from-to)	1215-1224
Number of pages	10
Journal	Human Molecular Genetics
Volume	25
Issue number	6
DOIs	https://doi.org/10.1093/hmg/ddw002
State	Published - 15 Mar 2016
Externally published	Yes

Bibliographical note

Publisher Copyright:
© The Author 2016. Published by Oxford University Press. All rights reserved.

Funding

The NHPAC study is supported by the National Basic Research Program of China (973 Program 2012CB524900), and the National Natural Science Foundation of China (30930081, 81170734, 81321062, and 81471013). We are grateful to all participants of the NHAPC, and also thank our colleagues at the laboratory and local CDC staffs of Beijing and Shanghai for their assistance with data collection. MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-001079, UL1-TR-000040, and DK063491. Funding for MESA SHARe genotyping was provided by NHLBI Contract N02-HL-64278. MESA SHARe genotyping was performed as Affymetrix (Santa Clara, California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affymetrix Genome-Wide Human SNP Array 6.0. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute grant HL105756. The authors thank all investigators, staff and participants from the studies of NHAPC and MESA cohorts for their contributions to this work. We appreciate the European PUFA GWAS data sharing by the CHARGE Consortium.

Funders	Funder number
Broad Institute of Harvard and MIT
CDC staffs of Beijing and Shanghai
CHARGE Consortium
European PUFA GWAS
NHAPC
National Heart, Lung, and Blood Institute	UL1-TR-001079, UL1-TR-000040, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, HL105756, N01-HC-95160, N01-HC-95169, N01-HC-95159, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, DK063491, R01HL064278
Array BioPharma
National Natural Science Foundation of China	30930081, 81471013, 81321062, 81170734
National Basic Research Program of China (973 Program)	2012CB524900

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10.1093/hmg/ddw002

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Hu, Y., Li, H., Lu, L., Manichaikul, A., Zhu, J., Chen, I. Y. D., Sun, L., Liang, S., Siscovick, D. S., Steffen, L. M., Tsai, M. Y., Rich, S. S., Lemaitre, R. N., & Lin, X. (2016). Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in chinese and european-ancestry populations. Human Molecular Genetics, 25(6), 1215-1224. https://doi.org/10.1093/hmg/ddw002

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title = "Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in chinese and european-ancestry populations",

abstract = "Epidemiological studies suggest that levels of n-3 and n-6 long-chain polyunsaturated fatty acids are associated with risk of cardio-metabolic outcomes across different ethnic groups. Recent genome-wide association studies in populations of European ancestry have identified several loci associated with plasma and/or erythrocyte polyunsaturated fatty acids. To identify additional novel loci, we carried out a genome-wide association study in two population-based cohorts consisting of 3521 Chinese participants, followed by a trans-ethnic meta-analysis with meta-analysis results from 8962 participants of European ancestry. Four novel loci (MYB, AGPAT4, DGAT2 and PPT2) reached genome-wide significance in the trans-ethnic meta-analysis (log10(Bayes Factor) ≥ 6). Of them, associations of MYB and AGPAT4 with docosatetraenoic acid (log10(Bayes Factor) = 11.5 and 8.69, respectively) also reached genome-wide significance in the Chinese-specific genome-wide association analyses (P = 4.15 × 10-14 and 4.30 × 10-12, respectively), while associations of DGAT2 with gamma-linolenic acid (log10(Bayes Factor) = 6.16) and of PPT2 with docosapentaenoic acid (log10(Bayes Factor) = 6.24) were nominally significant in both Chinese- and European-specific genome-wide association analyses (P ≤ 0.003). We also confirmed previously reported loci including FADS1, NTAN1, NRBF2, ELOVL2 and GCKR. Different effect sizes in FADS1 and independent association signals in ELOVL2 were observed. These results provide novel insight into the genetic background of polyunsaturated fatty acids and their differences between Chinese and European populations.",

author = "Yao Hu and Huaixing Li and Ling Lu and Ani Manichaikul and Jingwen Zhu and Chen, {I. Yii Der} and Liang Sun and Shuang Liang and Siscovick, {David S.} and Steffen, {Lyn M.} and Tsai, {Michael Y.} and Rich, {Stephen S.} and Lemaitre, {Rozenn N.} and Xu Lin",

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Hu, Y, Li, H, Lu, L, Manichaikul, A, Zhu, J, Chen, IYD, Sun, L, Liang, S, Siscovick, DS, Steffen, LM, Tsai, MY, Rich, SS, Lemaitre, RN & Lin, X 2016, 'Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in chinese and european-ancestry populations', Human Molecular Genetics, vol. 25, no. 6, pp. 1215-1224. https://doi.org/10.1093/hmg/ddw002

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T1 - Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in chinese and european-ancestry populations

AU - Hu, Yao

AU - Li, Huaixing

AU - Lu, Ling

AU - Manichaikul, Ani

AU - Zhu, Jingwen

AU - Chen, I. Yii Der

AU - Sun, Liang

AU - Liang, Shuang

AU - Siscovick, David S.

AU - Steffen, Lyn M.

AU - Tsai, Michael Y.

AU - Rich, Stephen S.

AU - Lemaitre, Rozenn N.

AU - Lin, Xu

PY - 2016/3/15

Y1 - 2016/3/15

N2 - Epidemiological studies suggest that levels of n-3 and n-6 long-chain polyunsaturated fatty acids are associated with risk of cardio-metabolic outcomes across different ethnic groups. Recent genome-wide association studies in populations of European ancestry have identified several loci associated with plasma and/or erythrocyte polyunsaturated fatty acids. To identify additional novel loci, we carried out a genome-wide association study in two population-based cohorts consisting of 3521 Chinese participants, followed by a trans-ethnic meta-analysis with meta-analysis results from 8962 participants of European ancestry. Four novel loci (MYB, AGPAT4, DGAT2 and PPT2) reached genome-wide significance in the trans-ethnic meta-analysis (log10(Bayes Factor) ≥ 6). Of them, associations of MYB and AGPAT4 with docosatetraenoic acid (log10(Bayes Factor) = 11.5 and 8.69, respectively) also reached genome-wide significance in the Chinese-specific genome-wide association analyses (P = 4.15 × 10-14 and 4.30 × 10-12, respectively), while associations of DGAT2 with gamma-linolenic acid (log10(Bayes Factor) = 6.16) and of PPT2 with docosapentaenoic acid (log10(Bayes Factor) = 6.24) were nominally significant in both Chinese- and European-specific genome-wide association analyses (P ≤ 0.003). We also confirmed previously reported loci including FADS1, NTAN1, NRBF2, ELOVL2 and GCKR. Different effect sizes in FADS1 and independent association signals in ELOVL2 were observed. These results provide novel insight into the genetic background of polyunsaturated fatty acids and their differences between Chinese and European populations.

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Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in chinese and european-ancestry populations

Abstract

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Funding

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