title: Distinct variants at LIN28B influence growth in height from birth to adulthood.
abstract: We have studied the largely unknown genetic underpinnings of height growth by using a unique resource of longitudinal childhood height data available in Finnish population cohorts. After applying GWAS mapping of potential genes influencing pubertal height growth followed by further characterization of the genetic effects on complete postnatal growth trajectories, we have identified strong association between variants near LIN28B and pubertal growth (rs7759938; female p = 4.0 x 10(-9), male p = 1.5 x 10(-4), combined p = 5.0 x 10(-11), n = 5038). Analysis of growth during early puberty confirmed an effect on the timing of the growth spurt. Correlated SNPs have previously been implicated as influencing both adult stature and age at menarche, the same alleles associating with taller height and later age of menarche in other studies as with later pubertal growth here. Additionally, a partially correlated LIN28B SNP, rs314277, has been associated previously with final height. Testing both rs7759938 and rs314277 (pairwise r(2) = 0.29) for independent effects on postnatal growth in 8903 subjects indicated that the pubertal timing-associated marker rs7759938 affects prepubertal growth in females (p = 7 x 10(-5)) and final height in males (p = 5 x 10(-4)), whereas rs314277 has sex-specific effects on growth (p for interaction = 0.005) that were distinct from those observed at rs7759938. In conclusion, partially correlated variants at LIN28B tag distinctive, complex, and sex-specific height-growth-regulating effects, influencing the entire period of postnatal growth. These findings imply a critical role for LIN28B in the regulation of human growth.
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland. elisabeth.widen@helsinki.fi
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Widén
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.forename: Diana L
authors.initials: DL
authors.lastname: Cousminer
authors.forename: Ida
authors.initials: I
authors.lastname: Surakka
authors.forename: Tuuli
authors.initials: T
authors.lastname: Lappalainen
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.forename: Olli
authors.initials: O
authors.lastname: Raitakari
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Ulla
authors.initials: U
authors.lastname: Sovio
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Hartikainen
authors.forename: Anneli
authors.initials: A
authors.lastname: Pouta
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Clive
authors.initials: C
authors.lastname: Osmond
authors.forename: Eero
authors.initials: E
authors.lastname: Kajantie
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Jorma
authors.initials: J
authors.lastname: Viikari
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Chris
authors.initials: C
authors.lastname: Tyler-Smith
authors.forename: Nelson
authors.initials: N
authors.lastname: Freimer
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
mesh_terms: D000293:Adolescent; D000328:Adult; D001827:Body Height; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006128:Growth / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008572:Menarche / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins; D044465:White People / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C516326:LIN28B protein, human; D016601:RNA-Binding Proteins
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