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Fine mapping of genome-wide association study signals to identify genetic markers of the plasma triglyceride response to an omega-3 fatty acid supplementation

Fine mapping of genome-wide association study signals to identify genetic markers of the plasma triglyceride response to an omega-3 fatty acid supplementation
Fine mapping of genome-wide association study signals to identify genetic markers of the plasma triglyceride response to an omega-3 fatty acid supplementation
Background:Using a genome-wide association study (GWAS) approach, our group previously computed a genetic risk score (GRS) from single nucleotide polymorphisms (SNPs) of 10 loci that affect the plasma triglyceride (TG) response to an omega-3 (n–3) fatty acid (FA) supplementation.Objectives:The objective was to compute a novel and more refined GRS using fine mapping to include a large number of genetic variants.Methods:A total of 208 participants of the Fatty Acid Sensor (FAS) Study received 5 g fish oil/d, containing 1.9–2.2 g eicosapentaenoic acid and 1.1 g docosahexanoic acid, for 6 wk. Plasma TG concentrations were measured before and after supplementation. Dense genotyping and genotype imputation were used to refine mapping around GWAS hits. A GRS was computed by summing the number of at-risk alleles of tagging SNPs. Analyses were replicated in samples of the FINGEN study.Results:A total of 31 tagging SNPs associated with the TG response were used for GRS calculation in the FAS study. In a general linear model adjusted for age, sex, and body mass index, the GRS explained 49.73% of TG response variance (P < 0.0001). Nonresponders to the n–3 FA supplementation had a higher GRS than did responders. In the FINGEN replication study, the GRS explained 3.67% of TG response variance (P = 0.0006).Conclusions:Fine mapping proved to be effective to refine the previous GRS. Carrying increasing numbers of at-risk alleles of 31 SNPs confers a higher risk of being nonresponsive to n–3 FAs. The genetic profile therefore appears to be an important determinant of the plasma TG response to an n–3 FA supplementation and could be used to target those most likely to gain clinical benefit. This trial was registered at http://www.clinicaltrials.gov as NCT01343342.
0002-9165
Marcotte, Bastien Vallée
2560647f-b673-43a8-bbd6-982c6b2ce4ca
Guénard, Frédéric
117d1310-7011-4dfa-9166-fd465528ae72
Lemieux, Simone
306c7840-0ba4-45a2-ba56-7a6a6ff672b3
Couture, Patrick
13bc4649-4945-4ad3-beaf-5390e191ba63
Rudkowska, Iwona
5383f2a1-0d19-4d4b-9048-d5b0ef224452
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6
Minihane, Anne Marie
756f5703-6390-4359-bb04-f5790553d914
Vohl, Marie-Claude
35d2e22d-f3b9-4ecc-9861-03a1594e023e
Marcotte, Bastien Vallée
2560647f-b673-43a8-bbd6-982c6b2ce4ca
Guénard, Frédéric
117d1310-7011-4dfa-9166-fd465528ae72
Lemieux, Simone
306c7840-0ba4-45a2-ba56-7a6a6ff672b3
Couture, Patrick
13bc4649-4945-4ad3-beaf-5390e191ba63
Rudkowska, Iwona
5383f2a1-0d19-4d4b-9048-d5b0ef224452
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6
Minihane, Anne Marie
756f5703-6390-4359-bb04-f5790553d914
Vohl, Marie-Claude
35d2e22d-f3b9-4ecc-9861-03a1594e023e

Marcotte, Bastien Vallée, Guénard, Frédéric, Lemieux, Simone, Couture, Patrick, Rudkowska, Iwona, Calder, Philip, Minihane, Anne Marie and Vohl, Marie-Claude (2019) Fine mapping of genome-wide association study signals to identify genetic markers of the plasma triglyceride response to an omega-3 fatty acid supplementation. American Journal of Clinical Nutrition. (doi:10.1093/ajcn/nqy298).

Record type: Article

Abstract

Background:Using a genome-wide association study (GWAS) approach, our group previously computed a genetic risk score (GRS) from single nucleotide polymorphisms (SNPs) of 10 loci that affect the plasma triglyceride (TG) response to an omega-3 (n–3) fatty acid (FA) supplementation.Objectives:The objective was to compute a novel and more refined GRS using fine mapping to include a large number of genetic variants.Methods:A total of 208 participants of the Fatty Acid Sensor (FAS) Study received 5 g fish oil/d, containing 1.9–2.2 g eicosapentaenoic acid and 1.1 g docosahexanoic acid, for 6 wk. Plasma TG concentrations were measured before and after supplementation. Dense genotyping and genotype imputation were used to refine mapping around GWAS hits. A GRS was computed by summing the number of at-risk alleles of tagging SNPs. Analyses were replicated in samples of the FINGEN study.Results:A total of 31 tagging SNPs associated with the TG response were used for GRS calculation in the FAS study. In a general linear model adjusted for age, sex, and body mass index, the GRS explained 49.73% of TG response variance (P < 0.0001). Nonresponders to the n–3 FA supplementation had a higher GRS than did responders. In the FINGEN replication study, the GRS explained 3.67% of TG response variance (P = 0.0006).Conclusions:Fine mapping proved to be effective to refine the previous GRS. Carrying increasing numbers of at-risk alleles of 31 SNPs confers a higher risk of being nonresponsive to n–3 FAs. The genetic profile therefore appears to be an important determinant of the plasma TG response to an n–3 FA supplementation and could be used to target those most likely to gain clinical benefit. This trial was registered at http://www.clinicaltrials.gov as NCT01343342.

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Accepted/In Press date: 2 October 2018
e-pub ahead of print date: 8 January 2019

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Local EPrints ID: 427434
URI: https://eprints.soton.ac.uk/id/eprint/427434
ISSN: 0002-9165
PURE UUID: 4a08c41a-bb5f-4860-adac-683df06a1690

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Date deposited: 16 Jan 2019 17:30
Last modified: 21 May 2019 16:30

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Contributors

Author: Bastien Vallée Marcotte
Author: Frédéric Guénard
Author: Simone Lemieux
Author: Patrick Couture
Author: Iwona Rudkowska
Author: Philip Calder
Author: Anne Marie Minihane
Author: Marie-Claude Vohl

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