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Genome of The Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels.
Friday,2015-04-17 13:50 America/Los_Angeles — zdrager
| Title | Genome of The Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | van Leeuwen, EM, Karssen, LC, Deelen, J, Isaacs, A, Medina-Gómez, C, Mbarek, H, Kanterakis, A, Trompet, S, Postmus, I, Verweij, N, van Enckevort, DJ, Huffman, JE, White, CC, Feitosa, MF, Bartz, TM, Manichaikul, A, Joshi, PK, Peloso, GM, Deelen, P, van Dijk, F, Willemsen, G, de Geus, EJ, Milaneschi, Y, Penninx, BWJH, Francioli, LC, Menelaou, A, Pulit, SL, Rivadeneira, F, Hofman, A, Oostra, BA, Franco, OH, Leach, IMateo, Beekman, M, de Craen, AJM, Uh, H-W, Trochet, H, Hocking, LJ, Porteous, DJ, Sattar, N, Packard, CJ, Buckley, BM, Brody, JA, Bis, JC, Rotter, JI, Mychaleckyj, JC, Campbell, H, Duan, Q, Lange, LA, Wilson, JF, Hayward, C, Polasek, O, Vitart, V, Rudan, I, Wright, AF, Rich, SS, Psaty, BM, Borecki, IB, Kearney, PM, Stott, DJ, L Cupples, A, J Jukema, W, van der Harst, P, Sijbrands, EJ, Hottenga, J-J, Uitterlinden, AG, Swertz, MA, van Ommen, G-JB, de Bakker, PIW, P Slagboom, E, Boomsma, DI, Wijmenga, C, van Duijn, CM |
| Corporate/Institutional Authors | Genome of the Netherlands Consortium |
| Journal | Nat Commun |
| Volume | 6 |
| Pagination | 6065 |
| Date Published | 2015 |
| ISSN | 2041-1723 |
| Keywords | ATP-Binding Cassette Transporters, Cholesterol, Gene Frequency, Genetic Association Studies, Humans, Mutation, Missense, Netherlands |
| Abstract | <p>Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of The Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value <6.61 × 10(-4)), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C=0.135, βTC=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR.</p> |
| DOI | 10.1038/ncomms7065 |
| Alternate Journal | Nat Commun |
| PubMed ID | 25751400 |
| PubMed Central ID | PMC4366498 |
| Grant List | 095831 / / Wellcome Trust / United Kingdom 1RC2 MH089951 / MH / NIMH NIH HHS / United States 1RC2 MH089995 / MH / NIMH NIH HHS / United States 284167 / / European Research Council / International 2R01LM010098 / LM / NLM NIH HHS / United States 5R01DK06833603 / DK / NIDDK NIH HHS / United States 5R01DK07568102 / DK / NIDDK NIH HHS / United States 5R01HL08770003 / HL / NHLBI NIH HHS / United States AG023629 / AG / NIA NIH HHS / United States CZD/16/6 / / Chief Scientist Office / United Kingdom CZD/16/6/4 / / Chief Scientist Office / United Kingdom HHSN268200800007C / / PHS HHS / United States HHSN268200960009C / / PHS HHS / United States HHSN268201200036C / / PHS HHS / United States HL-54776 / HL / NHLBI NIH HHS / United States HL080295 / HL / NHLBI NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States HL103612 / HL / NHLBI NIH HHS / United States HL105756 / HL / NHLBI NIH HHS / United States MC_PC_U127561128 / / Medical Research Council / United Kingdom MH081802 / MH / NIMH NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01-HC-95159 / HC / NHLBI NIH HHS / United States N01-HC-95160 / HC / NHLBI NIH HHS / United States N01-HC-95161 / HC / NHLBI NIH HHS / United States N01-HC-95162 / HC / NHLBI NIH HHS / United States N01-HC-95163 / HC / NHLBI NIH HHS / United States N01-HC-95164 / HC / NHLBI NIH HHS / United States N01-HC-95165 / HC / NHLBI NIH HHS / United States N01-HC-95166 / HC / NHLBI NIH HHS / United States N01-HC-95167 / HC / NHLBI NIH HHS / United States N01-HC-95168 / HC / NHLBI NIH HHS / United States N01-HC-95169 / HC / NHLBI NIH HHS / United States N01HC55222 / HC / NHLBI NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N02.HL.6.4278 / HL / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States R01 DK089256 / DK / NIDDK NIH HHS / United States R01 HD042157-01A1 / HD / NICHD NIH HHS / United States R01 HL117078 / HL / NHLBI NIH HHS / United States R01 LM010098 / LM / NLM NIH HHS / United States R01-HL-087700 / HL / NHLBI NIH HHS / United States R01-HL-088215 / HL / NHLBI NIH HHS / United States R01HL071051 / HL / NHLBI NIH HHS / United States R01HL071205 / HL / NHLBI NIH HHS / United States R01HL071250 / HL / NHLBI NIH HHS / United States R01HL071251 / HL / NHLBI NIH HHS / United States R01HL071252 / HL / NHLBI NIH HHS / United States R01HL071258 / HL / NHLBI NIH HHS / United States R01HL071259 / HL / NHLBI NIH HHS / United States RR-024156 / RR / NCRR NIH HHS / United States U24 MH068457-06 / MH / NIMH NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States / / Medical Research Council / United Kingdom |