Author
MERINO, JORDI - Massachusetts General Hospital | |
DASHTI, HASSAN - Massachusetts General Hospital | |
LI, SHERLY - University Of Cambridge | |
SARNOWSKI, CHLOE - Boston University School Of Public Health | |
JUSTICE, ANNE - University Of North Carolina | |
GRAFF, MISA - University Of North Carolina | |
PAPOUTSAKIS, CONSTANTINA - Academy Of Nutrition And Dietetics | |
SMITH, CAREN - Tufts University | |
DEDOUSSIS, GEORGE - Harokopio University Of Athens | |
LEMAITRE, ROZENN - University Of Washington | |
WOJCZYNSKI, MARY - Washington University School Of Medicine | |
MANNISTO, SATU - University Of Helsinki | |
NGWA, JULIUS - Boston University School Of Public Health | |
KHO, MINJUNG - University Of Michigan | |
AHLUWALIA, TARUNVEER - University Of Copenhagen | |
PERVJAKOVA, NATALIA - University Of Helsinki | |
HOUSTON, DENISE - Wake Forest School Of Medicine | |
BOUCHARD, CLAUDE - Pennington Biomedical Research Center | |
HUANG, TAO - Nanyang Technological University | |
ORHO-MELANDER, MARJU - Lund University | |
FRAZIER-WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC) | |
MOOK-KANAMORI, DENNIS - Leiden University Medical Center | |
PERUSSE, LOUIS - Laval University | |
PENNELL, CRAIG - University Of Western Australia | |
DE VRIES, PAUL - University Of Texas Health Science Center | |
VOORTMAN, TRUDY - Erasmus Medical Center | |
LI, OLIVIA - Hospital For Sick Children (SICKKIDS) | |
KANONI, STAVROULA - Queen Mary University Of London | |
ROSE, LYNDA - Brigham & Women'S Hospital | |
LEHTIMAKI, TERHO - University Of Tampere | |
ZHAO, JING - University Of Cambridge | |
FEITOSA, MARY - Washington University School Of Medicine | |
LUAN, JIAN'AN - University Of Cambridge | |
MCKEOWN, NICOLA - Tufts University | |
SMITH, JENNIFER - University Of Michigan | |
HANSEN, TORBEN - University Of Copenhagen | |
EKLUND, NIINA - University Of Helsinki | |
NALLS, MICHAEL - National Institute On Aging (NIA, NIH) | |
RANKINEN, TUOMO - Pennington Biomedical Research Center | |
HUANG, JINYAN - Shanghai Institute Of Technology | |
HERNANDEZ, DENA - National Institute On Aging (NIA, NIH) | |
SCHULZ, CHRISTINA - Lund University | |
MANICHAKUL, ANI - University Of Virginia | |
LI-GAO, RUIFANG - Leiden University | |
VOHL, MARIE - Laval University | |
WANG, CAROL - University Of Western Australia | |
VAN ROOIJ, FRANK - Erasmus Medical Center | |
SHIN, JEAN - Hospital For Sick Children (SICKKIDS) | |
KALAFATI, IOANNA - Harokopio University Of Athens | |
DAY, FELIX - University Of Cambridge | |
RIDKER, PAUL - Brigham & Women'S Hospital | |
KAHONEN, MIKA - University Of Tampere | |
SISCOVICK, DAVID - New York Academy Of Medicine | |
LANGENBERG, CLAUDIA - University Of Cambridge | |
ZHAO, WEI - University Of Michigan | |
ASTRUP, ARNE - University Of Copenhagen | |
KNEKT, PAUL - University Of Helsinki | |
GARCIA, MELISSA - National Institute On Aging (NIA, NIH) | |
RAO, D - Washington University School Of Medicine | |
QI, QIBIN - Albert Einstein College Of Medicine | |
FERRUCCI, LUIGI - National Institute On Aging (NIA, NIH) | |
ERICSON, ULRIKA - Lund University | |
BLANGERO, JOHN - University Of Texas Rio Grande Valley | |
HOFMAN, ALBERT - Erasmus Medical Center | |
PAUSOVA, ZDENKA - Hospital For Sick Children (SICKKIDS) | |
WAREHAM, NICK - University Of Cambridge | |
KARDIA, SHARON - University Of Michigan | |
PEDERSON, OLUF - University Of Copenhagen | |
JULA, ANTTI - University Of Helsinki | |
CURRAN, JOANNE - University Of Texas Rio Grande Valley | |
ZILLIKENS, M - Erasmus Medical Center | |
VIIKARI, JORMA - University Of Turku | |
FOROUHI, NITA - University Of Cambridge | |
ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University | |
LIESKE, JOHN - Mayo Clinic | |
RISSANEN, HARRI - University Of Helsinki | |
UITTERLINDEN, ANDRE - Erasmus Medical Center | |
RAITAKARI, OLLI - University Of Turku | |
KIEFTE-DE JONG, JESSICA - Erasmus Medical Center | |
DUPUIS, JOSEE - Boston University School Of Public Health | |
ROTTER, JEROME - Harbor-Ucla Medical Center | |
NORTH, KARI - University Of North Carolina | |
SCOTT, ROBERT - University Of Cambridge | |
PROVINCE, MICHAEL - Washington University School Of Medicine | |
PEROLA, MARKUS - University Of Helsinki | |
CUPPLES, L - Boston University School Of Public Health | |
TURNER, STEPHEN - Mayo Clinic | |
SORENSON, THORKILD - University Of Copenhagen | |
SALOMAA, VEIKKO - University Of Helsinki | |
LIU, YONGMEI - Wake Forest University | |
SUNG, YUN - Washington University School Of Medicine | |
BANDINELLI, STEFANIA - Azienda Sanitaria Di Firenze | |
RICH, STEPHEN - University Of Virginia | |
LYYTIKAINEN, LEO - University Of Tampere | |
CHASMAN, DANIEL - Brigham & Women'S Hospital | |
CHU, AUDREY - Brigham & Women'S Hospital | |
TANAKA, TOSHIKO - National Institute On Aging (NIA, NIH) |
Submitted to: Molecular Psychiatry
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 4/10/2018 Publication Date: 7/9/2018 Citation: Merino, J., Dashti, H., Li, S., Sarnowski, C., Justice, A., Graff, M., Papoutsakis, C., Smith, C., Dedoussis, G., Lemaitre, R., Wojczynski, M., Mannisto, S., Ngwa, J., Kho, M., Ahluwalia, T., Pervjakova, N., Houston, D., Bouchard, C., Huang, T., Orho-Melander, M., Frazier-Wood, A., Mook-Kanamori, D., Perusse, L., Pennell, C., De Vries, P., Voortman, T., Li, O., Kanoni, S., Rose, L., Lehtimaki, T., Zhao, J.H., Feitosa, M., Luan, J., McKeown, N., Smith, J., Hansen, T., Eklund, N., Nalls, M., Rankinen, T., Huang, J., Hernandez, D., Schulz, C.A., Manichakul, A., Li-Gao, R., Vohl, M.C., Wang, C., Van Rooij, F., Shin, J., Kalafati, I., Day, F., Ridker, P., Kahonen, M., Siscovick, D., Langenberg, C., Zhao, W., Astrup, A., Knekt, P., Garcia, M., Rao, D.C., Qi, Q., Ferrucci, L., Ericson, U., Blangero, J., Hofman, A., Pausova, Z., Wareham, N., Kardia, S., Pederson, O., Jula, A., Curran, J., Zillikens, M.C., Viikari, J., Forouhi, N., Ordovas, J., Lieske, J., Rissanen, H., Uitterlinden, A., Raitakari, O., Kiefte-De Jong, J., Dupuis, J., Rotter, J., North, K., Scott, R., Province, M., Perola, M., Cupples, L., Turner, S., Sorenson, T., Salomaa, V., Liu, Y., Sung, Y.J., Bandinelli, S., Rich, S., Lyytikainen, L.P., Chasman, D., Chu, A., 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. https://doi.org/10.1038/s41380-018-0079-4. DOI: https://doi.org/10.1038/s41380-018-0079-4 Interpretive Summary: The macronutrient content of our diet refers to the relative contributions of fat, carbohydrate, and protein to overall intake. Macronutrient intake is a modifiable risk factor for complex metabolic diseases, but we do not know why people choose different dietary macronutrient intakes. While there are environmental factors that predict macronutrient intake, there may also be innate genetic factors. To discover whether this is the case, we used data from over 20 studies across Europe and North America and scanned the genome for loci where variation associates with macronutrient intake. We found associations with loci in or near four genes: in FGF21 with intake of all three macronutrients, in RARB with carbohydrate intake, and in FTO and DRAM1 with protein intake. The functions of FGF21 and DRAM1 are poorly understood and should be examined in future studies, however FTO is the most well known genetic risk factor for obesity, and RARB is expressed in the central nervous system. Together these highlight the role of macronutrient intake in obesity risk, and the importance of behavioral factors in diseases related to food intake, respectively. If replicated and validated, this study may provide important information for predicting disease risk, and/or understanding the associations of macronutrients with disease risk. Technical 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 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. |