Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium

Hassan S Dashti; Torben Hansen; Arne Astrup; Oluf Borbye Pedersen; Thorkild I.A. Sørensen; Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium

doi:10.1038/s41380-018-0079-4

Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium

Hassan S Dashti, Torben Hansen, Arne Astrup, Oluf Borbye Pedersen, Thorkild I.A. Sørensen, Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium

22 Citations (Scopus)

Abstract

Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10⁻⁶) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.

Original language	English
Journal	Molecular Psychiatry
Volume	24
Pages (from-to)	1920–1932
Number of pages	13
ISSN	1359-4184
DOIs	https://doi.org/10.1038/s41380-018-0079-4
Publication status	Published - 1 Dec 2019

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Dashti, H. S., Hansen, T., Astrup, A., Pedersen, O. B., Sørensen, T. I. A., & Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium (2019). Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Molecular Psychiatry, 24, 1920–1932. https://doi.org/10.1038/s41380-018-0079-4

Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. / Dashti, Hassan S; Hansen, Torben; Astrup, Arne et al.
In: Molecular Psychiatry, Vol. 24, 01.12.2019, p. 1920–1932.

Research output: Contribution to journal › Journal article › Research › peer-review

Dashti, HS, Hansen, T, Astrup, A, Pedersen, OB , Sørensen, TIA & Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium 2019, 'Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium', Molecular Psychiatry, vol. 24, pp. 1920–1932. https://doi.org/10.1038/s41380-018-0079-4

Dashti HS, Hansen T, Astrup A, Pedersen OB , Sørensen TIA, Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium. Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Molecular Psychiatry. 2019 Dec 1;24:1920–1932. doi: 10.1038/s41380-018-0079-4

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abstract = "Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10−6) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.",

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AU - Sarnowski, Chloé

AU - Justice, Anne E

AU - Graff, Misa

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AU - Smith, Caren E

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AU - Frazier-Wood, Alexis C

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AU - Hansen, Torben

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AU - Manichaikul, Ani

AU - Li-Gao, Ruifang

AU - Vohl, Marie Claude

AU - Wang, Carol A

AU - van Rooij, Frank J A

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N2 - Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10−6) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.

AB - Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10−6) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.

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ER -

Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium

Abstract

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