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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

Merino, J, Dashti, HS, Li, SX, Sarnowski, C, Justice, AE, Graff, M, Papoutsakis, C, Smith, CE, Dedoussis, GV, Lemaitre, RN, Wojczynski, MK, Mannisto, S, Ngwa, JS, Kho, M, Ahluwalia, TS, Pervjakova, N, Houston, DK, Bouchard, C, Huang, T, Orho-Melander, M, Frazier-Wood, AC, Mook-Kanamori, DO, Perusse, L, Pennell, CE, de Vries, PS, Voortman, T, Li, O, Kanoni, S, Rose, LM, Lehtimaki, T, Zhao, JH, Feitosa, MF, Luan, J, McKeown, NM, Smith, JA, Hansen, T, Eklund, N, Nalls, MA, Rankinen, T, Huang, J, Hernandez, DG, Schulz, CA, Manichaikul, A, Li-Gao, R, Vohl, MC, Wang, CA, van Rooij, FJA, Shin, J, Kalafati, IP, Day, F, Ridker, PM, Kahonen, M, Siscovick, DS, Langenberg, C, Zhao, W, Astrup, A, Knekt, P, Garcia, M, Rao, DC, Qi, Q, Ferrucci, L, Ericson, U, Blangero, J, Hofman, A, Pausova, Z, Mikkila, V, Wareham, NJ, Kardia, SLR, Pedersen, O, Jula, A, Curran, JE, Zillikens, MC, Viikari, JS, Forouhi, NG, Ordovas, JM, Lieske, JC, Rissanen, H, Uitterlinden, AG, Raitakari, OT, Kiefte-de Jong, JC, Dupuis, J, Rotter, JI, North, KE, Scott, RA, Province, MA, Perola, M, Cupples, LA, Turner, ST, Sorensen, TIA, Salomaa, V, Liu, Y, Sung, YJ, Qi, L, Bandinelli, S, Rich, SS, de Mutsert, R, Tremblay, A, Oddy, WH ORCID: 0000-0002-6119-7017, Franco, OH, Paus, T, Florez, JC, Deloukas, P, Lyytikainen, LP, Chasman, DI, Chu, AY and Tanaka, T 2018 , '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, no. July , pp. 1-13 , 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 -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.

Item Type: Article
Authors/Creators:Merino, J and Dashti, HS and Li, SX and Sarnowski, C and Justice, AE and Graff, M and Papoutsakis, C and Smith, CE and Dedoussis, GV and Lemaitre, RN and Wojczynski, MK and Mannisto, S and Ngwa, JS and Kho, M and Ahluwalia, TS and Pervjakova, N and Houston, DK and Bouchard, C and Huang, T and Orho-Melander, M and Frazier-Wood, AC and Mook-Kanamori, DO and Perusse, L and Pennell, CE and de Vries, PS and Voortman, T and Li, O and Kanoni, S and Rose, LM and Lehtimaki, T and Zhao, JH and Feitosa, MF and Luan, J and McKeown, NM and Smith, JA and Hansen, T and Eklund, N and Nalls, MA and Rankinen, T and Huang, J and Hernandez, DG and Schulz, CA and Manichaikul, A and Li-Gao, R and Vohl, MC and Wang, CA and van Rooij, FJA and Shin, J and Kalafati, IP and Day, F and Ridker, PM and Kahonen, M and Siscovick, DS and Langenberg, C and Zhao, W and Astrup, A and Knekt, P and Garcia, M and Rao, DC and Qi, Q and Ferrucci, L and Ericson, U and Blangero, J and Hofman, A and Pausova, Z and Mikkila, V and Wareham, NJ and Kardia, SLR and Pedersen, O and Jula, A and Curran, JE and Zillikens, MC and Viikari, JS and Forouhi, NG and Ordovas, JM and Lieske, JC and Rissanen, H and Uitterlinden, AG and Raitakari, OT and Kiefte-de Jong, JC and Dupuis, J and Rotter, JI and North, KE and Scott, RA and Province, MA and Perola, M and Cupples, LA and Turner, ST and Sorensen, TIA and Salomaa, V and Liu, Y and Sung, YJ and Qi, L and Bandinelli, S and Rich, SS and de Mutsert, R and Tremblay, A and Oddy, WH and Franco, OH and Paus, T and Florez, JC and Deloukas, P and Lyytikainen, LP and Chasman, DI and Chu, AY and Tanaka, T
Journal or Publication Title: Molecular Psychiatry
Publisher: Nature Publishing Group
ISSN: 1359-4184
DOI / ID Number: 10.1038/s41380-018-0079-4
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Copyright 2018 Macmillan Publishers Limited, part of Springer Nature

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