A novel common variant in DCST2 is associated with length in early life and height in adulthood

Autor: Rj, Valk, Kreiner-Møller E, Mn, Kooijman, Guxens M, Stergiakouli E, Sääf A, Jp, Bradfield, Geller F, Mg, Hayes, Dl, Cousminer, Körner A, Thiering E, Ja, Curtin, Myhre R, Huikari V, Joro R, Kerkhof M, Nm, Warrington, Pitkänen N, Ntalla I, Horikoshi M, Veijola R, Rm, Freathy, Yy, Teo, Sj, Barton, Dm, Evans, Jp, Kemp, St Pourcain B, Sm, Ring, Gd, Smith, Bergström A, Kull I, Hakonarson H, Fd, Mentch, Bisgaard H, Chawes B, Stokholm J, Waage J, Eriksen P, Sevelsted A, Melbye M, Cm, Duijn, Medina-Gomez C, Hofman A, Jc, Jongste, Hr, Taal, Ag, Uitterlinden, Ll, Armstrong, Eriksson J, Palotie A, Bustamante M, Estivill X, Jr, Gonzalez, Llop S, Kiess W, Mahajan A, Flexeder C, Cm, Tiesler, Cs, Murray, Simpson A, Magnus P, Sengpiel V, Al, Hartikainen, Keinanen-Kiukaanniemi S, Lewin A, Da Silva Couto Alves A, Ai, Blakemore, Jl, Buxton, Kaakinen M, Rodriguez A, Sebert S, Vaarasmaki M, Lakka T, Lindi V, Gehring U, Ds, Postma, Ang W, Jp, Newnham, Lp, Lyytikäinen, Pahkala K, Ot, Raitakari, Panoutsopoulou K, Zeggini E, Di, Boomsma, Groen-Blokhuis M, Ilonen J, Franke L, Jn, Hirschhorn, Th, Pers, Liang L, Huang J, Hocher B, Knip M, Sm, Saw, Jw, Holloway, Melén E, Sf, Grant, Feenstra B, Wl, Lowe, Widén E, Sergeyev E, Grallert H, Adnan Custovic, Jacobsson B, Jarvelin MR, Atalay M, Gh, Koppelman, Ce, Pennell, Niinikoski H, Gv, Dedoussis, Mi, Mccarthy, Tm, Frayling, Sunyer J, Nj, Timpson, Rivadeneira F, Bønnelykke K, Vw, Jaddoe
Přispěvatelé: Medical Research Council (MRC), Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Pediatrics, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, Gastroenterology & Hepatology, Epidemiology, Internal Medicine, Medical Oncology
Předmět:
Netherlands Twin Register (NTR)
Adult
Biochemistry & Molecular Biology
Genotype
Genetic Investigation of ANthropometric Traits (GIANT) Consortium
Quantitative Trait Loci
LOCI
Polymorphism
Single Nucleotide
DISEASE
Quantitative Trait
Heritable
Early Growth Genetics (EGG) Consortium
Databases
Genetic
Psychology
GLUCOCEREBROSIDASE MUTATIONS
TOOL
Humans
LOW-BIRTH-WEIGHT
GENOME-WIDE ASSOCIATION
DC-STAMP
Alleles
Genetic Association Studies
Medicinsk genetik
Adaptor Proteins
Signal Transducing
Genetics & Heredity
Psykologi
Science & Technology
IMPUTED DATA
Association Studies Articles
Age Factors
Infant
Newborn
Computational Biology
Genetic Variation
Membrane Proteins
Reproducibility of Results
11 Medical And Health Sciences
06 Biological Sciences
GENE
Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium
C420 Human Genetics
Body Height
Phenotype
Institut für Ernährungswissenschaft
epidemiology
Medical Genetics
Life Sciences & Biomedicine
biological
GROWTH-RETARDATION
Zdroj: Europe PubMed Central
van der Valk, R J P, Kreiner-Moller, E, Kooijman, M N, Guxens, M, Stergiakouli, E, Saaf, A, Bradfield, J P, Geller, F, Hayes, M G, Cousminer, D L, Koerner, A, Thiering, E, Curtin, J A, Myhre, R, Huikari, V, Joro, R, Kerkhof, M, Warrington, N M, Pitkanen, N, Ntalla, I, Horikoshi, M, Veijola, R, Freathy, R M, Teo, Y, Barton, S J, Evans, D M, Kemp, J P, St Pourcain, B, Ring, S M, Smith, G D, Bergstrom, A, Kull, I, Hakonarson, H, Mentch, F D, Bisgaard, H, Chawes, B, Stokholm, J, Waage, J, Eriksen, P, Sevelsted, A, Melbye, M, van Duijn, C M, Medina-Gomez, C, Hofman, A, de Jongste, J C, Taal, H R, Uitterlinden, A G, Armstrong, L L, Eriksson, J, Palotie, A, Bustamante, M, Estivill, X, Gonzalez, J R, Llop, S, Kiess, W, Mahajan, A, Flexeder, C, Tiesler, C M T, Murray, C S, Simpson, A, Magnus, P, Sengpiel, V, Hartikainen, A, Keinanen-Kiukaanniemi, S, Lewin, A, Alves, A D S C, Blakemore, A I, Buxton, J L, Kaakinen, M, Rodriguez, A, Sebert, S, Vaarasmaki, M, Lakka, T, Lindi, V, Gehring, U, Postma, D S, Ang, W, Newnham, J P, Lyytikainen, L, Pahkala, K, Raitakari, O T, Panoutsopoulou, K, Zeggini, E, Boomsma, D I, Groen-Blokhuis, M M, Ilonen, J, Franke, L, Hirschhorn, J N, Pers, T H, Liang, L, Huang, J, Hocher, B, Knip, M, Saw, S, Holloway, J W, Melen, E, Grant, S F A, Feenstra, B, Lowe, W L, Widen, E, Sergeyev, E, Grallert, H, Custovic, A, Jacobsson, B, Jarvelin, M, Atalay, M, Koppelman, G H, Pennell, C E, Niinikoski, H, Dedoussis, G V, McCarthy, M I, Frayling, T M, Sunyer, J, Timpson, N J, Rivadeneira, F, Bonnelykke, K & Jaddoe, V W V 2015, ' A novel common variant in DCST2 is associated with length in early life and height in adulthood ', Human Molecular Genetics, vol. 24, no. 4, pp. 1155-1168 . https://doi.org/10.1093/hmg/ddu510
Hum. Mol. Genet. 24, 1155-1168 (2015)
Human Molecular Genetics
Human Molecular Genetics, 24(4), 1155-1168. Oxford University Press
ISSN: 0964-6906
DOI: 10.1093/hmg/ddu510
Popis: 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 seven independent top single nucleotide polymorphisms (SNPs) (P < 1 x 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine 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; beta = 0.046, SE = 0.008, P = 2.46 x 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 x 10(-4)) and adult height (N = 127 513; P = 1.45 x 10(-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.
Databáze: OpenAIRE
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