@article{fa282723dedd4ce7a97c332beaab02a5,
title = "Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci",
abstract = "Few studies have explored the impact of rare variants (minor allele frequency < 1%) on highly heritable plasma metabolites identified in metabolomic screens. The Finnish population provides an ideal opportunity for such explorations, given the multiple bottlenecks and expansions that have shaped its history, and the enrichment for many otherwise rare alleles that has resulted. Here, we report genetic associations for 1391 plasma metabolites in 6136 men from the late-settlement region of Finland. We identify 303 novel association signals, more than one third at variants rare or enriched in Finns. Many of these signals identify genes not previously implicated in metabolite genome-wide association studies and suggest mechanisms for diseases and disease-related traits.",
author = "FinnGen and Xianyong Yin and Chan, {Lap Sum} and Debraj Bose and Jackson, {Anne U.} and Peter VandeHaar and Locke, {Adam E.} and Christian Fuchsberger and Stringham, {Heather M.} and Ryan Welch and Ketian Yu and {Fernandes Silva}, Lilian and Service, {Susan K.} and Daiwei Zhang and Hector, {Emily C.} and Erica Young and Liron Ganel and Indraniel Das and Haley Abel and Erdos, {Michael R.} and Bonnycastle, {Lori L.} and Johanna Kuusisto and Stitziel, {Nathan O.} and Hall, {Ira M.} and Wagner, {Gregory R.} and Samuli Ripatti and Aarno Palotie and Jian Kang and Jean Morrison and Burant, {Charles F.} and Collins, {Francis S.} and Samuli Ripatti and Aarno Palotie and Freimer, {Nelson B.} and Mohlke, {Karen L.} and Scott, {Laura J.} and Xiaoquan Wen and Fauman, {Eric B.} and Markku Laakso and Michael Boehnke",
note = "Funding Information: We thank the participants in the METSIM and FinnGen studies and the FinnGen study investigators. We thank Hyun Min Kang and Matthew W. Mitchell for their expertise and consultation in the genotype integration and metabolomics data processing. This work was supported by the National Institutes of Health (NIH) under awards U01 DK062370 (M.B. and A.E.L.), R35 GM138121 (X.Q.W.), R01 DK119380 (X.Q.W.), R01 GM124061 (J.Kang, E.C.H., and D.W.Z.), R01 DA048993 (J.Kang), R01 MH105561 (J.Kang), P01 HL151328 (N.O.S), R01 HL131961 (N.O.S), UM1 HG008853 (I.H., N.O.S., L.G., and A.E.L.), R01 DK093757 (K.L.M.), U01 DK105561 (K.L.M.), T32 HL007081 (E.Y.), and UL1 TR002345 (E.Y.). X.Y.Y. was supported by an American Diabetes Association Postdoctoral Fellowship (1-19-PDF-061) and a University of Michigan Precision Health Scholarship. M.L. was supported by the Academy of Finland (grant no. 321428) and the Sigrid Juselius Foundation. S.R. was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (grant no. 312062 and 336820), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, University of Helsinki HiLIFE Fellow and Grand Challenge grants, and Horizon 2020 Research and Innovation Programme (grant no. 101016775 “INTERVENE”). A.P. was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (grant no. 312074 and 336824). F.S.C., M.R.E., and L.L.B. were supported by the NIH Intramural Research Program of the National Human Genome Research Institute (ZIA HG000024). Funding Information: We thank the participants in the METSIM and FinnGen studies and the FinnGen study investigators. We thank Hyun Min Kang and Matthew W. Mitchell for their expertise and consultation in the genotype integration and metabolomics data processing. This work was supported by the National Institutes of Health (NIH) under awards U01 DK062370 (M.B. and A.E.L.), R35 GM138121 (X.Q.W.), R01 DK119380 (X.Q.W.), R01 GM124061 (J.Kang, E.C.H., and D.W.Z.), R01 DA048993 (J.Kang), R01 MH105561 (J.Kang), P01 HL151328 (N.O.S), R01 HL131961 (N.O.S), UM1 HG008853 (I.H., N.O.S., L.G., and A.E.L.), R01 DK093757 (K.L.M.), U01 DK105561 (K.L.M.), T32 HL007081 (E.Y.), and UL1 TR002345 (E.Y.). X.Y.Y. was supported by an American Diabetes Association Postdoctoral Fellowship (1-19-PDF-061) and a University of Michigan Precision Health Scholarship. M.L. was supported by the Academy of Finland (grant no. 321428) and the Sigrid Juselius Foundation. S.R. was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (grant no. 312062 and 336820), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, University of Helsinki HiLIFE Fellow and Grand Challenge grants, and Horizon 2020 Research and Innovation Programme (grant no. 101016775 “INTERVENE”). A.P. was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (grant no. 312074 and 336824). F.S.C., M.R.E., and L.L.B. were supported by the NIH Intramural Research Program of the National Human Genome Research Institute (ZIA HG000024). Funding Information: A.E.L. is an employee and stockholder of Regeneron Pharmaceuticals. L.G. is an employee of Genentech, Inc. and stockholder of Roche. N.O.S. has received research funding from Regeneron Pharmaceuticals unrelated to this work. G.R.W. is a stockholder of Metabolon, Inc. E.B.F. is an employee and stockholder of Pfizer. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-29143-5",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
number = "1",
}