Citation
Merino, Jordi; Dashti, Hassan S.; Li, Sherly X.; Sarnowski, Chloe; Justice, Anne E.; Graff, Mariaelisa; Papoutsakis, Constantina; Smith, Caren E.; Dedoussis, George; & Lemaitre, Rozenn N., et al. (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(12), 1920-1932. PMCID: PMC6326896Abstract
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 x 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.URL
http://dx.doi.org/10.1038/s41380-018-0079-4Reference Type
Journal ArticleYear Published
2019Journal Title
Molecular PsychiatryAuthor(s)
Merino, JordiDashti, Hassan S.
Li, Sherly X.
Sarnowski, Chloe
Justice, Anne E.
Graff, Mariaelisa
Papoutsakis, Constantina
Smith, Caren E.
Dedoussis, George
Lemaitre, Rozenn N.
Wojczynski, Mary K.
Mannisto, Satu
Ngwa, Julius S.
Kho, Minjung
Ahluwalia, Tarunveer S.
Pervjakova, Natalia
Houston, Denise K.
Bouchard, Claude
Huang, Tao
Orho-Melander, Marju
Frazier-Wood, Alexis C.
Mook-Kanamori, Dennis O.
Perusse, Louis
Pennell, Craig E.
de Vries, Paul S.
Voortman, Trudy
Li, Olivia
Kanoni, Stavroula
Rose, Lynda M.
Lehtimaki, Terho
Zhao, Jing Hua
Feitosa, Mary F.
Luan, Jian'an
McKeown, Nicola M.
Smith, Jennifer A.
Hansen, Torben
Eklund, Niina
Nalls, Mike A.
Rankinen, Tuomo
Huang, Jinyan
Hernandez, Dena
Schulz, Christina-Alexandra
Manichaikul, Ani
Li-Gao, Ruifang
Vohl, Marie-Claude
Wang, Carol A.
van Rooij, Frank J. A.
Shin, Jean
Kalafati, Ioanna P.
Day, Felix R.
Ridker, Paul M.
Kahonen, Mika
Siscovick, David S.
Langenberg, Claudia
Zhao, Wei
Astrup, Arne
Knekt, Paul
Garcia, Melissa E.
Rao, Dabeeru C.
Qi, Qibin
Ferrucci, Luigi
Ericson, Ulrika
Blangero, John
Hofman, Albert
Pausova, Zdenka
Mikkila, Vera
Wareham, Nicholas J.
Kardia, Sharon L. R.
Pedersen, Oluf
Jula, Antti M.
Curran, Joanne E.
Zillikens, M. Carola
Viikari, Jorma S.
Forouhi, Nita G.
Ordóñez, José M.
Lieske, John C.
Rissanen, Harri
Uitterlinden, Andre G.
Raitakari, Olli T.
Kiefte-de Jong, Jessica C.
Dupuis, Josee
Rotter, Jerome I.
North, Kari E.
Scott, Robert A.
Province, Michael A.
Perola, Markus
Cupples, L. Adrienne
Turner, Stephen T.
Sorensen, Thorkild I. A.
Salomaa, Veikko
Liu, Yongmei
Sung, Yun J.
Qi, Lu
Bandinelli, Stefania
Rich, Stephen S.
de Mutsert, Renee
Tremblay, Angelo
Oddy, Wendy H.
Franco, Oscar H.
Paus, Tomas
Florez, Jose C.
Deloukas, Panos
Lyytikainen, Leo-Pekka
Chasman, Daniel I.
Chu, Audrey Y.
Tanaka, Toshiko