Novel signals and polygenic score for height are associated with pubertal growth traits in Southwestern American Indians
Abstract Most genetic variants associated with adult height have been identified through large genome-wide association studies (GWASs) in European-ancestry cohorts. However, it is unclear how these variants influence linear growth during adolescence. This study uses anthropometric and genotypic data...
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| Veröffentlicht in: | Human molecular genetics 2024-05, Vol.33 (11), p.981-990 |
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| container_title | Human molecular genetics |
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| creator | Ramírez-Luzuriaga, Maria J Kobes, Sayuko Hsueh, Wen-Chi Baier, Leslie J Hanson, Robert L |
| description | Abstract
Most genetic variants associated with adult height have been identified through large genome-wide association studies (GWASs) in European-ancestry cohorts. However, it is unclear how these variants influence linear growth during adolescence. This study uses anthropometric and genotypic data from a longitudinal study conducted in an American Indian community in Arizona between 1965–2007. Growth parameters (i.e. height, velocity, and timing of growth spurt) were derived from the Preece-Baines growth model, a parametric growth curve fitted to longitudinal height data, in 787 participants with height measurements spanning the whole period of growth. Heritability estimates suggested that genetic factors could explain 25% to 71% of the variance of pubertal growth traits. We performed a GWAS of growth parameters, testing their associations with 5 077 595 imputed or directly genotyped variants. Six variants associated with height at peak velocity (P |
| doi_str_mv | 10.1093/hmg/ddae030 |
| format | Article |
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Most genetic variants associated with adult height have been identified through large genome-wide association studies (GWASs) in European-ancestry cohorts. However, it is unclear how these variants influence linear growth during adolescence. This study uses anthropometric and genotypic data from a longitudinal study conducted in an American Indian community in Arizona between 1965–2007. Growth parameters (i.e. height, velocity, and timing of growth spurt) were derived from the Preece-Baines growth model, a parametric growth curve fitted to longitudinal height data, in 787 participants with height measurements spanning the whole period of growth. Heritability estimates suggested that genetic factors could explain 25% to 71% of the variance of pubertal growth traits. We performed a GWAS of growth parameters, testing their associations with 5 077 595 imputed or directly genotyped variants. Six variants associated with height at peak velocity (P < 5 × 10-8, adjusted for sex, birth year and principal components). Implicated genes include NUDT3, previously associated with adult height, and PACSIN1. Two novel variants associated with duration of growth spurt (P < 5 × 10-8) in LOC105375344, an uncharacterized gene with unknown function. We finally examined the association of growth parameters with a polygenic score for height derived from 9557 single nucleotide polymorphisms (SNPs) identified in the GIANT meta-analysis for which genotypic data were available for the American Indian study population. Height polygenic score was correlated with the magnitude and velocity of height growth that occurred before and at the peak of the adolescent growth spurt, indicating overlapping genetic architecture, with no influence on the timing of adolescent growth.</description><identifier>ISSN: 0964-6906</identifier><identifier>ISSN: 1460-2083</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/ddae030</identifier><identifier>PMID: 38483351</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adolescent ; Arizona ; Body Height - genetics ; Child ; Female ; Genome-Wide Association Study ; Genotype ; Humans ; Indians, North American - genetics ; Longitudinal Studies ; Male ; Multifactorial Inheritance - genetics ; Polymorphism, Single Nucleotide ; Puberty - genetics</subject><ispartof>Human molecular genetics, 2024-05, Vol.33 (11), p.981-990</ispartof><rights>Published by Oxford University Press 2024. 2024</rights><rights>Published by Oxford University Press 2024.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c315t-c73b7eb5fe41190319cc1707d463098f6470c2833f22f1a289a4ce517715af353</cites><orcidid>0000-0003-2912-5256</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38483351$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ramírez-Luzuriaga, Maria J</creatorcontrib><creatorcontrib>Kobes, Sayuko</creatorcontrib><creatorcontrib>Hsueh, Wen-Chi</creatorcontrib><creatorcontrib>Baier, Leslie J</creatorcontrib><creatorcontrib>Hanson, Robert L</creatorcontrib><title>Novel signals and polygenic score for height are associated with pubertal growth traits in Southwestern American Indians</title><title>Human molecular genetics</title><addtitle>Hum Mol Genet</addtitle><description>Abstract
Most genetic variants associated with adult height have been identified through large genome-wide association studies (GWASs) in European-ancestry cohorts. However, it is unclear how these variants influence linear growth during adolescence. This study uses anthropometric and genotypic data from a longitudinal study conducted in an American Indian community in Arizona between 1965–2007. Growth parameters (i.e. height, velocity, and timing of growth spurt) were derived from the Preece-Baines growth model, a parametric growth curve fitted to longitudinal height data, in 787 participants with height measurements spanning the whole period of growth. Heritability estimates suggested that genetic factors could explain 25% to 71% of the variance of pubertal growth traits. We performed a GWAS of growth parameters, testing their associations with 5 077 595 imputed or directly genotyped variants. Six variants associated with height at peak velocity (P < 5 × 10-8, adjusted for sex, birth year and principal components). Implicated genes include NUDT3, previously associated with adult height, and PACSIN1. Two novel variants associated with duration of growth spurt (P < 5 × 10-8) in LOC105375344, an uncharacterized gene with unknown function. We finally examined the association of growth parameters with a polygenic score for height derived from 9557 single nucleotide polymorphisms (SNPs) identified in the GIANT meta-analysis for which genotypic data were available for the American Indian study population. Height polygenic score was correlated with the magnitude and velocity of height growth that occurred before and at the peak of the adolescent growth spurt, indicating overlapping genetic architecture, with no influence on the timing of adolescent growth.</description><subject>Adolescent</subject><subject>Arizona</subject><subject>Body Height - genetics</subject><subject>Child</subject><subject>Female</subject><subject>Genome-Wide Association Study</subject><subject>Genotype</subject><subject>Humans</subject><subject>Indians, North American - genetics</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Multifactorial Inheritance - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Puberty - genetics</subject><issn>0964-6906</issn><issn>1460-2083</issn><issn>1460-2083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMoun6cvEtOIkjdpGmb5iiLHwuiB_Vcsum0jbRJTVJX_72RXT16Gl54eGfmQeiUkitKBJt3QzuvawmEkR00o1lBkpSUbBfNiCiypBCkOECH3r8RQouM8X10wMqsZCynM_T5aD-gx163RvYeS1Pj0fZfLRitsFfWAW6swx3otgtYxii9t0rLADVe69DhcVqBC7LHrbPrmIOTOnisDX62U-jW4AM4g68HcFpJg5em1tL4Y7TXxI1wsp1H6PX25mVxnzw83S0X1w-JYjQPieJsxWGVN5BRKgijQinKCa-zghFRNkXGiUrjM02aNlSmpZCZgpxyTnPZsJwdoYtN7-js-xSPqQbtFfS9NGAnX6Ui57TgIicRvdygylnvHTTV6PQg3VdFSfWjuoqqq63qSJ9ti6fVAPUf--s2AucbwE7jv03f48WJAw</recordid><startdate>20240518</startdate><enddate>20240518</enddate><creator>Ramírez-Luzuriaga, Maria J</creator><creator>Kobes, Sayuko</creator><creator>Hsueh, Wen-Chi</creator><creator>Baier, Leslie J</creator><creator>Hanson, Robert L</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2912-5256</orcidid></search><sort><creationdate>20240518</creationdate><title>Novel signals and polygenic score for height are associated with pubertal growth traits in Southwestern American Indians</title><author>Ramírez-Luzuriaga, Maria J ; Kobes, Sayuko ; Hsueh, Wen-Chi ; Baier, Leslie J ; Hanson, Robert L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c315t-c73b7eb5fe41190319cc1707d463098f6470c2833f22f1a289a4ce517715af353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adolescent</topic><topic>Arizona</topic><topic>Body Height - genetics</topic><topic>Child</topic><topic>Female</topic><topic>Genome-Wide Association Study</topic><topic>Genotype</topic><topic>Humans</topic><topic>Indians, North American - genetics</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Multifactorial Inheritance - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Puberty - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ramírez-Luzuriaga, Maria J</creatorcontrib><creatorcontrib>Kobes, Sayuko</creatorcontrib><creatorcontrib>Hsueh, Wen-Chi</creatorcontrib><creatorcontrib>Baier, Leslie J</creatorcontrib><creatorcontrib>Hanson, Robert L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Human molecular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ramírez-Luzuriaga, Maria J</au><au>Kobes, Sayuko</au><au>Hsueh, Wen-Chi</au><au>Baier, Leslie J</au><au>Hanson, Robert L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel signals and polygenic score for height are associated with pubertal growth traits in Southwestern American Indians</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Hum Mol Genet</addtitle><date>2024-05-18</date><risdate>2024</risdate><volume>33</volume><issue>11</issue><spage>981</spage><epage>990</epage><pages>981-990</pages><issn>0964-6906</issn><issn>1460-2083</issn><eissn>1460-2083</eissn><abstract>Abstract
Most genetic variants associated with adult height have been identified through large genome-wide association studies (GWASs) in European-ancestry cohorts. However, it is unclear how these variants influence linear growth during adolescence. This study uses anthropometric and genotypic data from a longitudinal study conducted in an American Indian community in Arizona between 1965–2007. Growth parameters (i.e. height, velocity, and timing of growth spurt) were derived from the Preece-Baines growth model, a parametric growth curve fitted to longitudinal height data, in 787 participants with height measurements spanning the whole period of growth. Heritability estimates suggested that genetic factors could explain 25% to 71% of the variance of pubertal growth traits. We performed a GWAS of growth parameters, testing their associations with 5 077 595 imputed or directly genotyped variants. Six variants associated with height at peak velocity (P < 5 × 10-8, adjusted for sex, birth year and principal components). Implicated genes include NUDT3, previously associated with adult height, and PACSIN1. Two novel variants associated with duration of growth spurt (P < 5 × 10-8) in LOC105375344, an uncharacterized gene with unknown function. We finally examined the association of growth parameters with a polygenic score for height derived from 9557 single nucleotide polymorphisms (SNPs) identified in the GIANT meta-analysis for which genotypic data were available for the American Indian study population. Height polygenic score was correlated with the magnitude and velocity of height growth that occurred before and at the peak of the adolescent growth spurt, indicating overlapping genetic architecture, with no influence on the timing of adolescent growth.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>38483351</pmid><doi>10.1093/hmg/ddae030</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-2912-5256</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Arizona Body Height - genetics Child Female Genome-Wide Association Study Genotype Humans Indians, North American - genetics Longitudinal Studies Male Multifactorial Inheritance - genetics Polymorphism, Single Nucleotide Puberty - genetics |
| title | Novel signals and polygenic score for height are associated with pubertal growth traits in Southwestern American Indians |
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