Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.
Wei ZhaoAsif RasheedEmmi TikkanenJung-Jin LeeAdam S ButterworthJoanna M M HowsonThemistocles L AssimesRajiv ChowdhuryMarju Orho-MelanderScott DamrauerAeron SmallSenay AsmaMinako ImamuraToshimasa YamauchJohn C ChambersPeng ChenBishwa R SapkotaNabi ShahSehrish JabeenPraveen SurendranYingchang LuWeihua ZhangAtif ImranShahid AbbasFaisal MajeedKevin TrindadeNadeem QamarNadeem Hayyat MallickZia YaqoobTahir SaghirSyed Nadeem Hasan RizviAnis MemonSyed Zahed RasheedFazal-Ur-Rehman MemonKhalid MehmoodNaveeduddin AhmedIrshad Hussain Qureshinull Tanveer-Us-SalamWasim IqbalUzma MalikNarinder MehraJane Z KuoWayne H-H SheuXiuqing GuoChao A HsiungJyh-Ming J JuangKent D TaylorYi-Jen HungWen-Jane LeeThomas QuertermousI-Te LeeChih-Cheng HsuErwin P BottingerSarju RalhanYik Ying TeoTzung-Dau WangDewan S AlamEmanuele Di AngelantonioSteve EpsteinSune F NielsenBørge G NordestgaardAnne Tybjaerg-HansenRobin Youngnull nullMarianne BennRuth Frikke-SchmidtPia R Kamstrupnull nullnull nullnull nullJ Wouter JukemaNaveed SattarRoelof SmitRen-Hua ChungKae-Woei LiangSonia AnandDharambir K SangheraSamuli RipattiRuth J F LoosJaspal S KoonerE Shyong TaiJerome I RotterYii-Der Ida ChenPhilippe FrossardShiro MaedaTakashi KadowakiMuredach ReillyGuillaume PareOlle MelanderVeikko SalomaaDaniel J RaderJohn DaneshBenjamin F VoightDanish SaleheenPublished in: Nature genetics (2017)
To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D-CHD analysis identified eight variants-two of which are coding-where T2D and CHD associations appear to colocalize, including a new joint T2D-CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.