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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2010
|
| Online Access: | http://hdl.handle.net/1721.1/59321 |
| _version_ | 1811075736626266112 |
|---|---|
| author | Peltonen, Leena Elliott, Paul McCarthy, Mark I. Jarvelin, Marjo-Riitta Widen, Elisabeth 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 Hartikaninen, Anna-Liisa Freimer, Nelson B. |
| author2 | Broad Institute of MIT and Harvard |
| author_facet | Broad Institute of MIT and Harvard Peltonen, Leena Elliott, Paul McCarthy, Mark I. Jarvelin, Marjo-Riitta Widen, Elisabeth 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 Hartikaninen, Anna-Liisa Freimer, Nelson B. |
| author_sort | Peltonen, Leena |
| collection | MIT |
| 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. |
| first_indexed | 2024-09-23T10:10:57Z |
| format | Article |
| id | mit-1721.1/59321 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:10:57Z |
| publishDate | 2010 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/593212022-09-30T19:25:45Z Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966 Peltonen, Leena Elliott, Paul McCarthy, Mark I. Jarvelin, Marjo-Riitta Widen, Elisabeth 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 Hartikaninen, Anna-Liisa Freimer, Nelson B. Broad Institute of MIT and Harvard Peltonen, Leena Peltonen, Leena 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. University Hospital Oulu, Biocenter Academy of Finland (project grant 104781) Academy of Finland (project grant 120315) Academy of Finland. Center of Excellence in Complex Disease Genetics University of Oulu National Heart, Lung, and Blood Institute (grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01)) Sixth Framework Programme (European Commission) (ENGAGE project grant agreement HEALTH-F4-2007-201413) Medical Research Council (Great Britain) (studentship grant G0500539) Medical Research Council (Great Britain) (centre grant G0600705) Wellcome Trust (project grant GR069224) Research Councils UK 2010-10-14T15:07:05Z 2010-10-14T15:07:05Z 2009-03 2008-09 Article http://purl.org/eprint/type/JournalArticle 1553-7404 http://hdl.handle.net/1721.1/59321 Sovio U, Bennett AJ, Millwood IY, Molitor J, O'Reilly PF, et al. (2009) Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966. PLoS Genet 5(3): e1000409. doi:10.1371/journal.pgen.1000409 19266077 en_US http://dx.doi.org/10.1371/journal.pgen.1000409 PLoS Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Peltonen, Leena Elliott, Paul McCarthy, Mark I. Jarvelin, Marjo-Riitta Widen, Elisabeth 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 Hartikaninen, Anna-Liisa Freimer, Nelson B. 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 |
| url | http://hdl.handle.net/1721.1/59321 |
| work_keys_str_mv | AT peltonenleena geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT elliottpaul geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT mccarthymarki geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT jarvelinmarjoriitta geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT widenelisabeth geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 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 hartikaninenannaliisa geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 AT freimernelsonb geneticdeterminantsofheightgrowthassessedlongitudinallyfrominfancytoadulthoodinthenorthernfinlandbirthcohort1966 |