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.

Authors:
Dr. ir. Trudy Voortman, PhD
Dr. ir. Trudy Voortman, PhD
Erasmus MC, University Medical Center, Rotterdam
nutrition, lifestyle, obesity, epidemiology
Rotterdam | Netherlands
Jordi Merino Hassan S Dashti Sherly X Li Chloé Sarnowski Anne E Justice Misa Graff Constantina Papoutsakis Caren E Smith George V Dedoussis Rozenn N Lemaitre Mary K Wojczynski Satu Männistö Julius S Ngwa Minjung Kho Tarunveer S Ahluwalia Natalia Pervjakova Denise K Houston Claude Bouchard Tao Huang Marju Orho-Melander Alexis C Frazier-Wood Dennis O Mook-Kanamori Louis Pérusse Craig E Pennell Paul S de Vries Olivia Li Stavroula Kanoni Lynda M Rose Terho Lehtimäki Jing Hua Zhao Mary F Feitosa Jian'an Luan Nicola M McKeown Jennifer A Smith Torben Hansen Niina Eklund Mike A Nalls Tuomo Rankinen Jinyan Huang Dena G Hernandez Christina-Alexandra Schulz Ani Manichaikul Ruifang Li-Gao Marie-Claude Vohl Carol A Wang Frank J A van Rooij Jean Shin Ioanna P Kalafati Felix Day Paul M Ridker Mika Kähönen David S Siscovick Claudia Langenberg Wei Zhao Arne Astrup Paul Knekt Melissa Garcia D C Rao Qibin Qi Luigi Ferrucci Ulrika Ericson John Blangero Albert Hofman Zdenka Pausova Vera Mikkilä Nick J Wareham Sharon L R Kardia Oluf Pedersen Antti Jula Joanne E Curran M Carola Zillikens Jorma S Viikari Nita G Forouhi José M Ordovás John C Lieske Harri Rissanen André G Uitterlinden Olli T Raitakari Jessica C Kiefte-de Jong Josée Dupuis Jerome I Rotter Kari E North Robert A Scott Michael A Province Markus Perola L Adrienne Cupples Stephen T Turner Thorkild I A Sørensen Veikko Salomaa Yongmei Liu Yun J Sung Lu Qi Stefania Bandinelli Stephen S Rich Renée de Mutsert Angelo Tremblay Wendy H Oddy Oscar H Franco Tomas Paus Jose C Florez Panos Deloukas Leo-Pekka Lyytikäinen Daniel I Chasman Audrey Y Chu Toshiko Tanaka

Mol Psychiatry 2019 Dec 9;24(12):1920-1932. Epub 2018 Jul 9.

Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.

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) 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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http://dx.doi.org/10.1038/s41380-018-0079-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326896PMC
December 2019
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