Cargando…
Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646138/ https://www.ncbi.nlm.nih.gov/pubmed/19266077 http://dx.doi.org/10.1371/journal.pgen.1000409 |
_version_ | 1782164824505974784 |
---|---|
author | 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 Peltonen, Leena Elliott, Paul McCarthy, Mark I. Jarvelin, Marjo-Riitta |
author_facet | 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 Peltonen, Leena Elliott, Paul McCarthy, Mark I. Jarvelin, Marjo-Riitta |
author_sort | Sovio, Ulla |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2646138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26461382009-03-06 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 Peltonen, Leena Elliott, Paul McCarthy, Mark I. Jarvelin, Marjo-Riitta PLoS Genet Research Article 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. Public Library of Science 2009-03-06 /pmc/articles/PMC2646138/ /pubmed/19266077 http://dx.doi.org/10.1371/journal.pgen.1000409 Text en Sovio et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article 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 Peltonen, 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 |
title | Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966 |
title_full | Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966 |
title_fullStr | Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966 |
title_full_unstemmed | Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966 |
title_short | Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966 |
title_sort | genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern finland birth cohort 1966 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646138/ https://www.ncbi.nlm.nih.gov/pubmed/19266077 http://dx.doi.org/10.1371/journal.pgen.1000409 |
work_keys_str_mv | AT sovioulla geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT bennettamandaj geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT millwoodionay geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT molitorjohn geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT oreillypaulf geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT timpsonnicholasj geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT kaakinenmarika geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT laitinenjaana geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT haukkajari geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT pillasdemetris geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT tzoulakiioanna geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT molitorjassy geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT hoggartclive geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT coinlachlanjm geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT whittakerjohn geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT poutaanneli geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT hartikainenannaliisa geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT freimernelsonb geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT widenelisabeth geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT peltonenleena geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT elliottpaul geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT mccarthymarki geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT jarvelinmarjoriitta geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 |