A novel common variant in DCST2 is associated with length in early life and height in adulthood
A novel common variant in DCST2 is associated with length in early life and height in adulthood
Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N=28,459). We identified 7 independent top SNPs (P<1x10-6) for birth length, of which 3 were novel and 4 were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The 3 novel SNPs were followed-up in 9 replication studies (Stage 2; N=11,995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1+2; ß=0.046, S.E.=0.008, P=2.46x10?8, explained variance=0.05%). Rs905938 was also associated with infant length (N=28,228; P=5.54x10-4) and adult height (N=127,513; P=1.45x10-5). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
1155-1168
van der Valk, R.J.P.
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Kreiner-Moller, E.
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Kooijman, M.N.
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Guxens, M.
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Stergiakouli, E.
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Saaf, A.
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Bradfield, J. P.
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Geller, F.
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Hayes, M.G.
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Cousminer, D.L.
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Korner, A.
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Thiering, E.
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Curtin, J.A.
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Myhre, R.
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Huikari, V.
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Joro, R.
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Kerkhof, M.
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Warrington, N.M.
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Pitkanen, N.
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Ntalla, I.
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Horikoshi, M.
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Veijola, R.
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Freathy, R.M.
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TEO, Y.-Y.
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Barton, S.J.
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Evans, D.M.
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Kemp, J.P.
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St Pourcain, B.
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Ring, S.M.
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Smith, G.D.
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Bergstrom, A.
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Kull, I.
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Hakonarson, H.
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Mentch, F.D.
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Bisgaard, H.
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Chawes, B.
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Stokholm, J.
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Waage, J.
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Eriksen, P.
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Sevelsted, A.
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van Duijn, C. M.
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Medina-Gomez, C.
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Hofman, A.
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Taal, H.R.
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Uitterlinden, A.G.
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Armstrong, L.L.
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Eriksson, J.
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Palotie, A.
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Gonzalez, J.R.
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Kiess, W.
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Mahajan, A.
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Flexeder, C.
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Tiesler, C.M.T.
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Murray, C. S.
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Simpson, A.
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Magnus, P.
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Sengpiel, V.
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Hartikainen, A.-L.
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Lewin, A.
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Da Silva Couto Alves, A.
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Blakemore, A.I.
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Buxton, J.L.
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Kaakinen, M.
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Rodriguez, A.
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Sebert, S.
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Vaarasmaki, M.
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Lakka, T.
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Gehring, U.
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Postma, D.S.
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Ang, W.
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Newnham, J.P.
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Lyytikainen, L.-P.
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Pahkala, K.
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Raitakari, O.T.
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Panoutsopoulou, K.
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Zeggini, E.
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Boomsma, D.I.
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Groen-Blokhuis, M.
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Ilonen, J.
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Franke, L.
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Hirschhorn, J.N.
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Pers, T.H.
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Liang, L.
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Huang, J.
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Hocher, B.
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Knip, M.
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Melen, E.
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Widen, E.
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Sergeyev, E.
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Grallert, H.
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Custovic, A.
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Jacobsson, B.
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Jaddoe, V.W.V.
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15 February 2015
van der Valk, R.J.P.
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Kreiner-Moller, E.
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Kooijman, M.N.
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Guxens, M.
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Stergiakouli, E.
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Saaf, A.
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Bradfield, J. P.
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Geller, F.
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Hayes, M.G.
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Cousminer, D.L.
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Korner, A.
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Thiering, E.
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Curtin, J.A.
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Myhre, R.
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Huikari, V.
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Joro, R.
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Kerkhof, M.
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Warrington, N.M.
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Pitkanen, N.
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Ntalla, I.
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Horikoshi, M.
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Veijola, R.
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Freathy, R.M.
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TEO, Y.-Y.
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Barton, S.J.
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Evans, D.M.
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Kemp, J.P.
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St Pourcain, B.
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Ring, S.M.
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Smith, G.D.
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Bergstrom, A.
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Kull, I.
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Hakonarson, H.
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Mentch, F.D.
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Bisgaard, H.
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Chawes, B.
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Stokholm, J.
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Waage, J.
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Eriksen, P.
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Sevelsted, A.
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van Duijn, C. M.
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Medina-Gomez, C.
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Armstrong, L.L.
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Eriksson, J.
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Palotie, A.
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Bustamante, M.
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Estivill, X.
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Gonzalez, J.R.
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Llop, S.
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Kiess, W.
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Mahajan, A.
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Flexeder, C.
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Tiesler, C.M.T.
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Murray, C. S.
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Magnus, P.
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Sengpiel, V.
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Hartikainen, A.-L.
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Lewin, A.
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Buxton, J.L.
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Kaakinen, M.
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Rodriguez, A.
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Sebert, S.
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Vaarasmaki, M.
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Lakka, T.
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Lindi, V.
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Gehring, U.
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Postma, D.S.
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Ang, W.
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Newnham, J.P.
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Lyytikainen, L.-P.
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Pahkala, K.
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Raitakari, O.T.
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Panoutsopoulou, K.
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Zeggini, E.
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Boomsma, D.I.
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Groen-Blokhuis, M.
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Ilonen, J.
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Franke, L.
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Hirschhorn, J.N.
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Pers, T.H.
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Liang, L.
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Huang, J.
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Hocher, B.
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Knip, M.
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Saw, S.-M.
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Holloway, J.W.
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Melen, E.
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Grant, S.F.A.
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Feenstra, B.
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Lowe, W.L.
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Widen, E.
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Sergeyev, E.
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Grallert, H.
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Custovic, A.
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Jacobsson, B.
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Jarvelin, M.-R.
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Atalay, M.
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Koppelman, G.H.
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Pennell, C.E.
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Niinikoski, H.
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Dedoussis, G.V.
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McCarthy, M.I.
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Frayling, T.M.
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Sunyer, J.
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Timpson, N.J.
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Rivadeneira, F.
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Bonnelykke, K.
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Jaddoe, V.W.V.
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