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

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

Journal: European journal of nutrition 2018;56(4):1477-1484

PMID: 26932504

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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 and P = 4.33 × 10, respectively), and a novel 20:0-associated locus at CERS4 (ceramide synthase 4) (P = 1.76 × 10). We also confirmed the previously reported association of FADS1/2-rs102275 with 18:0 (P = 1.12 × 10). 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.

Address: The Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China.; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.; Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, VA, USA.; Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.; The Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China. [email protected].

DOI: 10.1007/s00394-016-1193-1

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MeSH Terms: AMP Deaminase, Aged, Alleles, Asian People, China, Cholesterol, Delta-5 Fatty Acid Desaturase, Fatty Acid Desaturases, Fatty Acids, Female, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Genotyping Techniques, Humans, LIM-Homeodomain Proteins, Male, Middle Aged, Polymorphism, Single Nucleotide, Sphingosine N-Acyltransferase, Transcription Factors, Triglycerides, United States