摘要:
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.附注:
Merino, JordiDashti, Hassan SLi, Sherly XSarnowski, ChloeJustice, Anne EGraff, MisaPapoutsakis, ConstantinaSmith, Caren EDedoussis, George VLemaitre, Rozenn NWojczynski, Mary KMannisto, SatuNgwa, Julius SKho, MinjungAhluwalia, Tarunveer SPervjakova, NataliaHouston, Denise KBouchard, ClaudeHuang, TaoOrho-Melander, MarjuFrazier-Wood, Alexis CMook-Kanamori, Dennis OPerusse, LouisPennell, Craig Ede Vries, Paul SVoortman, TrudyLi, OliviaKanoni, StavroulaRose, Lynda MLehtimaki, TerhoZhao, Jing HuaFeitosa, Mary FLuan, Jian'anMcKeown, Nicola MSmith, Jennifer AHansen, TorbenEklund, NiinaNalls, Mike ARankinen, TuomoHuang, JinyanHernandez, Dena GSchulz, Christina-AlexandraManichaikul, AniLi-Gao, RuifangVohl, Marie-ClaudeWang, Carol Avan Rooij, Frank J AShin, JeanKalafati, Ioanna PDay, FelixRidker, Paul MKahonen, MikaSiscovick, David SLangenberg, ClaudiaZhao, WeiAstrup, ArneKnekt, PaulGarcia, MelissaRao, D CQi, QibinFerrucci, LuigiEricson, UlrikaBlangero, JohnHofman, AlbertPausova, ZdenkaMikkila, VeraWareham, Nick JKardia, Sharon L RPedersen, OlufJula, AnttiCurran, Joanne EZillikens, M CarolaViikari, Jorma SForouhi, Nita GOrdovas, Jose MLieske, John CRissanen, HarriUitterlinden, Andre GRaitakari, Olli TKiefte-de Jong, Jessica CDupuis, JoseeRotter, Jerome INorth, Kari EScott, Robert AProvince, Michael APerola, MarkusCupples, L AdrienneTurner, Stephen TSorensen, Thorkild I ASalomaa, VeikkoLiu, YongmeiSung, Yun JQi, LuBandinelli, StefaniaRich, Stephen Sde Mutsert, ReneeTremblay, AngeloOddy, Wendy HFranco, Oscar HPaus, TomasFlorez, Jose CDeloukas, PanosLyytikainen, Leo-PekkaChasman, Daniel IChu, Audrey YTanaka, ToshikoN01 HC025195/HC/WHI NIH HHS/T32 EY022303/EY/NEI NIH HHS/EnglandMol Psychiatry. 2018 Jul 9. pii: 10.1038/s41380-018-0079-4. doi: 10.1038/s41380-018-0079-4.