Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966

Ulla Sovio, Amanda J. Bennett, Iona Y. Millwood, John Molitor, Paul F. O'Reilly, Nicholas J. Timpson, Marika Kaakinen, Jaana Laitinen, Jari Haukka, Demetris Pillas, Ioanna Tzoulaki, Jassy Molitor, Clive Hoggart, Lachlan J. M. Coin, John Whittaker, Anneli Pouta, Anna-Liisa Hartikainen, Nelson B. Freimer, Elisabeth Widen, Leena PalotiePaul Elliott, Mark I. McCarthy, Marjo-Riitta Jarvelin

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Kuvaus

    "Recent genome-wide association (GWA) studies have identified dozens of common variants associated with adult height. However, it is unknown how these variants influence height growth during childhood. We derived peak height velocity in infancy (PHV1) and puberty (PHV2) and timing of pubertal height growth spurt from parametric growth curves fitted to longitudinal height growth data to test their association with known height variants. The study consisted of N = 3,538 singletons from the prospective Northern Finland Birth Cohort 1966 with genotype data and frequent height measurements (on average 20 measurements per person) from 0-20 years. Twenty-six of the 48 variants tested associated with adult height (p<0.05, adjusted for sex and principal components) in this sample, all in the same direction as in previous GWA scans. Seven SNPs in or near the genes HHIP, DLEU7, UQCC, SF3B4/SV2A, LCORL, and HIST1H1D associated with PHV1 and five SNPs in or near SOCS2, SF3B4/SV2A, C17orf67, CABLES1, and DOT1L with PHV2 (p<0.05). We formally tested variants for interaction with age (infancy versus puberty) and found biologically meaningful evidence for an age-dependent effect for the SNP in SOCS2 (p = 0.0030) and for the SNP in HHIP (p = 0.045). We did not have similar prior evidence for the association between height variants and timing of pubertal height growth spurt as we had for PHVs, and none of the associations were statistically significant after correction for multiple testing. The fact that in this sample, less than half of the variants associated with adult height had a measurable effect on PHV1 or PHV2 is likely to reflect limited power to detect these associations in this dataset. Our study is the first genetic association analysis on longitudinal height growth in a prospective cohort from birth to adulthood and gives grounding for future research on the genetic regulation of human height during different periods of growth."
    Alkuperäiskielienglanti
    LehtiPLoS Genetics
    Vuosikerta5
    Numero3
    Sivut-
    Sivumäärä8
    ISSN1553-7404
    DOI - pysyväislinkit
    TilaJulkaistu - 2009
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

    Tieteenalat

    • 311 Peruslääketieteet
    • 312 Kliiniset lääketieteet
    • 318 Lääketieteen bioteknologia
    • 217 Lääketieteen tekniikka
    • 118 Biotieteet

    Lainaa tätä

    Sovio, U., Bennett, A. J., Millwood, I. Y., Molitor, J., O'Reilly, P. F., Timpson, N. J., ... Jarvelin, M-R. (2009). Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966. PLoS Genetics, 5(3), -. https://doi.org/10.1371/journal.pgen.1000409
    Sovio, Ulla ; Bennett, Amanda J. ; Millwood, Iona Y. ; Molitor, John ; O'Reilly, Paul F. ; Timpson, Nicholas J. ; Kaakinen, Marika ; Laitinen, Jaana ; Haukka, Jari ; Pillas, Demetris ; Tzoulaki, Ioanna ; Molitor, Jassy ; Hoggart, Clive ; Coin, Lachlan J. M. ; Whittaker, John ; Pouta, Anneli ; Hartikainen, Anna-Liisa ; Freimer, Nelson B. ; Widen, Elisabeth ; Palotie, Leena ; Elliott, Paul ; McCarthy, Mark I. ; Jarvelin, Marjo-Riitta. / Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966. Julkaisussa: PLoS Genetics. 2009 ; Vuosikerta 5, Nro 3. Sivut -.
    @article{40e9761e3711475f877858fb269511d4,
    title = "Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966",
    abstract = "{"}Recent genome-wide association (GWA) studies have identified dozens of common variants associated with adult height. However, it is unknown how these variants influence height growth during childhood. We derived peak height velocity in infancy (PHV1) and puberty (PHV2) and timing of pubertal height growth spurt from parametric growth curves fitted to longitudinal height growth data to test their association with known height variants. The study consisted of N = 3,538 singletons from the prospective Northern Finland Birth Cohort 1966 with genotype data and frequent height measurements (on average 20 measurements per person) from 0-20 years. Twenty-six of the 48 variants tested associated with adult height (p<0.05, adjusted for sex and principal components) in this sample, all in the same direction as in previous GWA scans. Seven SNPs in or near the genes HHIP, DLEU7, UQCC, SF3B4/SV2A, LCORL, and HIST1H1D associated with PHV1 and five SNPs in or near SOCS2, SF3B4/SV2A, C17orf67, CABLES1, and DOT1L with PHV2 (p<0.05). We formally tested variants for interaction with age (infancy versus puberty) and found biologically meaningful evidence for an age-dependent effect for the SNP in SOCS2 (p = 0.0030) and for the SNP in HHIP (p = 0.045). We did not have similar prior evidence for the association between height variants and timing of pubertal height growth spurt as we had for PHVs, and none of the associations were statistically significant after correction for multiple testing. The fact that in this sample, less than half of the variants associated with adult height had a measurable effect on PHV1 or PHV2 is likely to reflect limited power to detect these associations in this dataset. Our study is the first genetic association analysis on longitudinal height growth in a prospective cohort from birth to adulthood and gives grounding for future research on the genetic regulation of human height during different periods of growth.{"}",
    keywords = "WIDE ASSOCIATION ANALYSIS, YOUNG MALE TWINS, CHILDHOOD, MODELS, HERITABILITY, VARIANTS, AGE, POPULATION, PUBERTY, STATURE, 311 Basic medicine, 312 Clinical medicine, 318 Medical biotechnology, 217 Medical engineering, 118 Biological sciences",
    author = "Ulla Sovio and Bennett, {Amanda J.} and Millwood, {Iona Y.} and John Molitor and O'Reilly, {Paul F.} and Timpson, {Nicholas J.} and Marika Kaakinen and Jaana Laitinen and Jari Haukka and Demetris Pillas and Ioanna Tzoulaki and Jassy Molitor and Clive Hoggart and Coin, {Lachlan J. M.} and John Whittaker and Anneli Pouta and Anna-Liisa Hartikainen and Freimer, {Nelson B.} and Elisabeth Widen and Leena Palotie and Paul Elliott and McCarthy, {Mark I.} and Marjo-Riitta Jarvelin",
    year = "2009",
    doi = "10.1371/journal.pgen.1000409",
    language = "English",
    volume = "5",
    pages = "--",
    journal = "PLoS Genetics",
    issn = "1553-7390",
    publisher = "PUBLIC LIBRARY OF SCIENCE",
    number = "3",

    }

    Sovio, U, Bennett, AJ, Millwood, IY, Molitor, J, O'Reilly, PF, Timpson, NJ, Kaakinen, M, Laitinen, J, Haukka, J, Pillas, D, Tzoulaki, I, Molitor, J, Hoggart, C, Coin, LJM, Whittaker, J, Pouta, A, Hartikainen, A-L, Freimer, NB, Widen, E, Palotie, L, Elliott, P, McCarthy, MI & Jarvelin, M-R 2009, 'Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966', PLoS Genetics, Vuosikerta 5, Nro 3, Sivut -. https://doi.org/10.1371/journal.pgen.1000409

    Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966. / Sovio, Ulla; Bennett, Amanda J.; Millwood, Iona Y.; Molitor, John; O'Reilly, Paul F.; Timpson, Nicholas J.; Kaakinen, Marika; Laitinen, Jaana; Haukka, Jari; Pillas, Demetris; Tzoulaki, Ioanna; Molitor, Jassy; Hoggart, Clive; Coin, Lachlan J. M.; Whittaker, John; Pouta, Anneli; Hartikainen, Anna-Liisa; Freimer, Nelson B.; Widen, Elisabeth; Palotie, Leena; Elliott, Paul; McCarthy, Mark I.; Jarvelin, Marjo-Riitta.

    julkaisussa: PLoS Genetics, Vuosikerta 5, Nro 3, 2009, s. -.

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    TY - JOUR

    T1 - Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966

    AU - Sovio, Ulla

    AU - Bennett, Amanda J.

    AU - Millwood, Iona Y.

    AU - Molitor, John

    AU - O'Reilly, Paul F.

    AU - Timpson, Nicholas J.

    AU - Kaakinen, Marika

    AU - Laitinen, Jaana

    AU - Haukka, Jari

    AU - Pillas, Demetris

    AU - Tzoulaki, Ioanna

    AU - Molitor, Jassy

    AU - Hoggart, Clive

    AU - Coin, Lachlan J. M.

    AU - Whittaker, John

    AU - Pouta, Anneli

    AU - Hartikainen, Anna-Liisa

    AU - Freimer, Nelson B.

    AU - Widen, Elisabeth

    AU - Palotie, Leena

    AU - Elliott, Paul

    AU - McCarthy, Mark I.

    AU - Jarvelin, Marjo-Riitta

    PY - 2009

    Y1 - 2009

    N2 - "Recent genome-wide association (GWA) studies have identified dozens of common variants associated with adult height. However, it is unknown how these variants influence height growth during childhood. We derived peak height velocity in infancy (PHV1) and puberty (PHV2) and timing of pubertal height growth spurt from parametric growth curves fitted to longitudinal height growth data to test their association with known height variants. The study consisted of N = 3,538 singletons from the prospective Northern Finland Birth Cohort 1966 with genotype data and frequent height measurements (on average 20 measurements per person) from 0-20 years. Twenty-six of the 48 variants tested associated with adult height (p<0.05, adjusted for sex and principal components) in this sample, all in the same direction as in previous GWA scans. Seven SNPs in or near the genes HHIP, DLEU7, UQCC, SF3B4/SV2A, LCORL, and HIST1H1D associated with PHV1 and five SNPs in or near SOCS2, SF3B4/SV2A, C17orf67, CABLES1, and DOT1L with PHV2 (p<0.05). We formally tested variants for interaction with age (infancy versus puberty) and found biologically meaningful evidence for an age-dependent effect for the SNP in SOCS2 (p = 0.0030) and for the SNP in HHIP (p = 0.045). We did not have similar prior evidence for the association between height variants and timing of pubertal height growth spurt as we had for PHVs, and none of the associations were statistically significant after correction for multiple testing. The fact that in this sample, less than half of the variants associated with adult height had a measurable effect on PHV1 or PHV2 is likely to reflect limited power to detect these associations in this dataset. Our study is the first genetic association analysis on longitudinal height growth in a prospective cohort from birth to adulthood and gives grounding for future research on the genetic regulation of human height during different periods of growth."

    AB - "Recent genome-wide association (GWA) studies have identified dozens of common variants associated with adult height. However, it is unknown how these variants influence height growth during childhood. We derived peak height velocity in infancy (PHV1) and puberty (PHV2) and timing of pubertal height growth spurt from parametric growth curves fitted to longitudinal height growth data to test their association with known height variants. The study consisted of N = 3,538 singletons from the prospective Northern Finland Birth Cohort 1966 with genotype data and frequent height measurements (on average 20 measurements per person) from 0-20 years. Twenty-six of the 48 variants tested associated with adult height (p<0.05, adjusted for sex and principal components) in this sample, all in the same direction as in previous GWA scans. Seven SNPs in or near the genes HHIP, DLEU7, UQCC, SF3B4/SV2A, LCORL, and HIST1H1D associated with PHV1 and five SNPs in or near SOCS2, SF3B4/SV2A, C17orf67, CABLES1, and DOT1L with PHV2 (p<0.05). We formally tested variants for interaction with age (infancy versus puberty) and found biologically meaningful evidence for an age-dependent effect for the SNP in SOCS2 (p = 0.0030) and for the SNP in HHIP (p = 0.045). We did not have similar prior evidence for the association between height variants and timing of pubertal height growth spurt as we had for PHVs, and none of the associations were statistically significant after correction for multiple testing. The fact that in this sample, less than half of the variants associated with adult height had a measurable effect on PHV1 or PHV2 is likely to reflect limited power to detect these associations in this dataset. Our study is the first genetic association analysis on longitudinal height growth in a prospective cohort from birth to adulthood and gives grounding for future research on the genetic regulation of human height during different periods of growth."

    KW - WIDE ASSOCIATION ANALYSIS

    KW - YOUNG MALE TWINS

    KW - CHILDHOOD

    KW - MODELS

    KW - HERITABILITY

    KW - VARIANTS

    KW - AGE

    KW - POPULATION

    KW - PUBERTY

    KW - STATURE

    KW - 311 Basic medicine

    KW - 312 Clinical medicine

    KW - 318 Medical biotechnology

    KW - 217 Medical engineering

    KW - 118 Biological sciences

    U2 - 10.1371/journal.pgen.1000409

    DO - 10.1371/journal.pgen.1000409

    M3 - Article

    VL - 5

    SP - -

    JO - PLoS Genetics

    JF - PLoS Genetics

    SN - 1553-7390

    IS - 3

    ER -