Meta-analysis of genome-wide association studies identifies three novel loci for saturated fatty acids in East Asians

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

doi:10.1007/s00394-016-1193-1

Meta-analysis of genome-wide association studies identifies three novel loci for saturated fatty acids in East Asians

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

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

6 Scopus citations

Abstract

Purpose: We aimed to characterize common genetic variants that influence saturated fatty acid concentrations in East Asians. Methods: Meta-analysis of genome-wide association studies for circulating SFAs was conducted in two population-based cohorts comprising 3521 participants of Chinese ancestry. Results: We identified two novel 14:0-associated loci at LMX1A (LIM homeobox transcription factor 1) and AMPD3 (AMP deaminase 3) (P = 5.08 × 10⁻⁹ and P = 4.33 × 10⁻⁸, respectively), and a novel 20:0-associated locus at CERS4 (ceramide synthase 4) (P = 1.76 × 10⁻¹⁰). We also confirmed the previously reported association of FADS1/2-rs102275 with 18:0 (P = 1.12 × 10⁻⁵). In addition, the A alleles of rs11042834 in AMPD3 and rs17159388 in CERS4 also exhibited evidence of associations with high-density lipoprotein cholesterol (P = 0.0162 and P = 0.0161, respectively). Conclusions: To our knowledge, this is the first GWAS analysis to examine SFA concentrations in East Asian populations. Our findings provide novel evidence that genetic variations of several genes from multiple pathways are associated with SFA concentrations in human body.

Original language	English (US)
Pages (from-to)	1477-1484
Number of pages	8
Journal	European Journal of Nutrition
Volume	56
Issue number	4
DOIs	https://doi.org/10.1007/s00394-016-1193-1
State	Published - Jun 1 2017

Bibliographical note

Funding Information:
The authors thank the participants of the MESA study, the Coordinating Center, MESA investigators, and study staff for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 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. This study is supported by the National High Technology Research and Development Program (863 Program 2009AA022704), the National Basic Research Program of China (973 Program 2012CB524900), the National Natural Science Foundation of China (30930081, 81170734 and 81021002), and the Chinese Academy of Sciences (KSCX2-EW-R-10 and SIBS2008006). 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 Affimetrix (Santa Clara, California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affimetrix Genome-Wide Human SNP Array 6.0.

Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.

Keywords

Arachidic acid
Chinese
Genome-wide association study
Lipids
Myristic acid

Publisher link

10.1007/s00394-016-1193-1

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374030

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Zhu, J., Manichaikul, A., Hu, Y., Chen, Y. D. I., Liang, S., Steffen, L. M., Rich, S. S., Tsai, M., Siscovick, D. S., Lemaitre, R. N., Li, H., & Lin, X. (2017). Meta-analysis of genome-wide association studies identifies three novel loci for saturated fatty acids in East Asians. European Journal of Nutrition, 56(4), 1477-1484. https://doi.org/10.1007/s00394-016-1193-1

@article{b20db708ce0343bd9784fda70dd45521,

title = "Meta-analysis of genome-wide association studies identifies three novel loci for saturated fatty acids in East Asians",

abstract = "Purpose: We aimed to characterize common genetic variants that influence saturated fatty acid concentrations in East Asians. Methods: Meta-analysis of genome-wide association studies for circulating SFAs was conducted in two population-based cohorts comprising 3521 participants of Chinese ancestry. Results: We identified two novel 14:0-associated loci at LMX1A (LIM homeobox transcription factor 1) and AMPD3 (AMP deaminase 3) (P = 5.08 × 10−9 and P = 4.33 × 10−8, respectively), and a novel 20:0-associated locus at CERS4 (ceramide synthase 4) (P = 1.76 × 10−10). We also confirmed the previously reported association of FADS1/2-rs102275 with 18:0 (P = 1.12 × 10−5). In addition, the A alleles of rs11042834 in AMPD3 and rs17159388 in CERS4 also exhibited evidence of associations with high-density lipoprotein cholesterol (P = 0.0162 and P = 0.0161, respectively). Conclusions: To our knowledge, this is the first GWAS analysis to examine SFA concentrations in East Asian populations. Our findings provide novel evidence that genetic variations of several genes from multiple pathways are associated with SFA concentrations in human body.",

keywords = "Arachidic acid, Chinese, Genome-wide association study, Lipids, Myristic acid",

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

note = "Funding Information: The authors thank the participants of the MESA study, the Coordinating Center, MESA investigators, and study staff for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 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. This study is supported by the National High Technology Research and Development Program (863 Program 2009AA022704), the National Basic Research Program of China (973 Program 2012CB524900), the National Natural Science Foundation of China (30930081, 81170734 and 81021002), and the Chinese Academy of Sciences (KSCX2-EW-R-10 and SIBS2008006). 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 Affimetrix (Santa Clara, California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affimetrix Genome-Wide Human SNP Array 6.0. Publisher Copyright: {\textcopyright} 2016, Springer-Verlag Berlin Heidelberg.",

year = "2017",

month = jun,

day = "1",

doi = "10.1007/s00394-016-1193-1",

language = "English (US)",

volume = "56",

pages = "1477--1484",

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TY - JOUR

T1 - Meta-analysis of genome-wide association studies identifies three novel loci for saturated fatty acids in East Asians

AU - Zhu, Jingwen

AU - Manichaikul, Ani

AU - Hu, Yao

AU - Chen, Yii Der I

AU - Liang, Shuang

AU - Steffen, Lyn M.

AU - Rich, Stephen S.

AU - Tsai, Michael

AU - Siscovick, David S.

AU - Lemaitre, Rozenn N.

AU - Li, Huaixing

AU - Lin, Xu

N1 - Funding Information: The authors thank the participants of the MESA study, the Coordinating Center, MESA investigators, and study staff for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 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. This study is supported by the National High Technology Research and Development Program (863 Program 2009AA022704), the National Basic Research Program of China (973 Program 2012CB524900), the National Natural Science Foundation of China (30930081, 81170734 and 81021002), and the Chinese Academy of Sciences (KSCX2-EW-R-10 and SIBS2008006). 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 Affimetrix (Santa Clara, California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affimetrix Genome-Wide Human SNP Array 6.0. Publisher Copyright: © 2016, Springer-Verlag Berlin Heidelberg.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Purpose: We aimed to characterize common genetic variants that influence saturated fatty acid concentrations in East Asians. Methods: Meta-analysis of genome-wide association studies for circulating SFAs was conducted in two population-based cohorts comprising 3521 participants of Chinese ancestry. Results: We identified two novel 14:0-associated loci at LMX1A (LIM homeobox transcription factor 1) and AMPD3 (AMP deaminase 3) (P = 5.08 × 10−9 and P = 4.33 × 10−8, respectively), and a novel 20:0-associated locus at CERS4 (ceramide synthase 4) (P = 1.76 × 10−10). We also confirmed the previously reported association of FADS1/2-rs102275 with 18:0 (P = 1.12 × 10−5). In addition, the A alleles of rs11042834 in AMPD3 and rs17159388 in CERS4 also exhibited evidence of associations with high-density lipoprotein cholesterol (P = 0.0162 and P = 0.0161, respectively). Conclusions: To our knowledge, this is the first GWAS analysis to examine SFA concentrations in East Asian populations. Our findings provide novel evidence that genetic variations of several genes from multiple pathways are associated with SFA concentrations in human body.

AB - Purpose: We aimed to characterize common genetic variants that influence saturated fatty acid concentrations in East Asians. Methods: Meta-analysis of genome-wide association studies for circulating SFAs was conducted in two population-based cohorts comprising 3521 participants of Chinese ancestry. Results: We identified two novel 14:0-associated loci at LMX1A (LIM homeobox transcription factor 1) and AMPD3 (AMP deaminase 3) (P = 5.08 × 10−9 and P = 4.33 × 10−8, respectively), and a novel 20:0-associated locus at CERS4 (ceramide synthase 4) (P = 1.76 × 10−10). We also confirmed the previously reported association of FADS1/2-rs102275 with 18:0 (P = 1.12 × 10−5). In addition, the A alleles of rs11042834 in AMPD3 and rs17159388 in CERS4 also exhibited evidence of associations with high-density lipoprotein cholesterol (P = 0.0162 and P = 0.0161, respectively). Conclusions: To our knowledge, this is the first GWAS analysis to examine SFA concentrations in East Asian populations. Our findings provide novel evidence that genetic variations of several genes from multiple pathways are associated with SFA concentrations in human body.

KW - Arachidic acid

KW - Chinese

KW - Genome-wide association study

KW - Lipids

KW - Myristic acid

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UR - http://www.scopus.com/inward/citedby.url?scp=84959358652&partnerID=8YFLogxK

U2 - 10.1007/s00394-016-1193-1

DO - 10.1007/s00394-016-1193-1

M3 - Article

C2 - 26932504

AN - SCOPUS:84959358652

VL - 56

SP - 1477

EP - 1484

JO - Zeitschrift fur Ernahrungswissenschaft

JF - Zeitschrift fur Ernahrungswissenschaft

SN - 1436-6207

IS - 4

ER -

Meta-analysis of genome-wide association studies identifies three novel loci for saturated fatty acids in East Asians

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