Dataset Information

Genome-wide association studies and fine-mapping identify genomic loci for n-3 and n-6 polyunsaturated fatty acids in Hispanic American and African American cohorts.

ABSTRACT: Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play critical roles in human health. Prior genome-wide association studies (GWAS) of n-3 and n-6 PUFAs in European Americans from the CHARGE Consortium have documented strong genetic signals in/near the FADS locus on chromosome 11. We performed a GWAS of four n-3 and four n-6 PUFAs in Hispanic American (n = 1454) and African American (n = 2278) participants from three CHARGE cohorts. Applying a genome-wide significance threshold of P < 5 × 10^-8, we confirmed association of the FADS signal and found evidence of two additional signals (in DAGLA and BEST1) within 200 kb of the originally reported FADS signal. Outside of the FADS region, we identified novel signals for arachidonic acid (AA) in Hispanic Americans located in/near genes including TMX2, SLC29A2, ANKRD13D and POLD4, and spanning a > 9 Mb region on chromosome 11 (57.5 Mb ~ 67.1 Mb). Among these novel signals, we found associations unique to Hispanic Americans, including rs28364240, a POLD4 missense variant for AA that is common in CHARGE Hispanic Americans but absent in other race/ancestry groups. Our study sheds light on the genetics of PUFAs and the value of investigating complex trait genetics across diverse ancestry populations.

SUBMITTER: Yang C

PROVIDER: S-EPMC10432561 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Genome-wide association studies and fine-mapping identify genomic loci for n-3 and n-6 polyunsaturated fatty acids in Hispanic American and African American cohorts.

Yang Chaojie C Veenstra Jenna J Bartz Traci M TM Pahl Matthew C MC Hallmark Brian B Chen Yii-Der Ida YI Westra Jason J Steffen Lyn M LM Brown Christopher D CD Siscovick David D Tsai Michael Y MY Wood Alexis C AC Rich Stephen S SS Smith Caren E CE O'Connor Timothy D TD Mozaffarian Dariush D Grant Struan F A SFA Chilton Floyd H FH Tintle Nathan L NL Lemaitre Rozenn N RN Manichaikul Ani A

Communications biology 20230816 1

Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play critical roles in human health. Prior genome-wide association studies (GWAS) of n-3 and n-6 PUFAs in European Americans from the CHARGE Consortium have documented strong genetic signals in/near the FADS locus on chromosome 11. We performed a GWAS of four n-3 and four n-6 PUFAs in Hispanic American (n = 1454) and African American (n = 2278) participants from three CHARGE cohorts. Applying a genome-wide significance threshold ...[more]

PMID: 37587153

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Project description:ObjectiveTo assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).DesignPooled analysis.Data sourcesA consortium of 19 studies from 12 countries identified up to May 2020.Study selectionProspective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.Data extraction and synthesisEach participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis.Main outcome measuresPrimary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2 and <75% of baseline rate.Results25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I2=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I2=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I2=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 v <60 years), estimated glomerular filtration rate (60-89 v ≥90 mL/min/1.73 m2), hypertension, diabetes, and coronary heart disease at baseline.ConclusionsHigher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.

Dataset Information

Genome-wide association studies and fine-mapping identify genomic loci for n-3 and n-6 polyunsaturated fatty acids in Hispanic American and African American cohorts.

Publications

Genome-wide association studies and fine-mapping identify genomic loci for n-3 and n-6 polyunsaturated fatty acids in Hispanic American and African American cohorts.

Similar Datasets

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