Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
28921393
TITLE
Genome-wide compound heterozygote analysis highlights alleles associated with adult height in Europeans.
ABSTRACT
Adult height is the most widely genetically studied common trait in humans; however, the trait variance explainable by currently known height-associated single nucleotide polymorphisms (SNPs) identified from the previous genome-wide association studies (GWAS) is yet far from complete given the high heritability of this complex trait. To exam if compound heterozygotes (CH) may explain extra height variance, we conducted a genome-wide analysis to screen for CH in association with adult height in 10,631 Dutch Europeans enriched with extremely tall people, using our recently developed method implemented in the software package CollapsABEL. The analysis identified six regions (3q23, 5q35.1, 6p21.31, 6p21.33, 7q21.2, and 9p24.3), where multiple pairs of SNPs as CH showed genome-wide significant association with height (P < 1.67 × 10(-10)). Of those, 9p24.3 represents a novel region influencing adult height, whereas the others have been highlighted in the previous GWAS on height based on analysis of individual SNPs. A replication analysis in 4080 Australians of European ancestry confirmed the significant CH-like association at 9p24.3 (P < 0.05). Together, the collapsed genotypes at these six loci explained 2.51% of the height variance (after adjusting for sex and age), compared with 3.23% explained by the 14 top-associated SNPs at 14 loci identified by traditional GWAS in the same data set (P < 5 × 10(-8)). Overall, our study empirically demonstrates that CH plays an important role in adult height and may explain a proportion of its "missing heritability". Moreover, our findings raise promising expectations for other highly polygenic complex traits to explain missing heritability identifiable through CH-like associations.
DATE PUBLISHED
2017 Sep 18
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2017/03/13
accepted 2017/08/26
entrez 2017/09/19 06:00
pubmed 2017/09/19 06:00
medline 2017/09/19 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Zhong K Zhong Kaiyin K Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Zhu G Zhu Gu G Queensland Institute of Medical Research, Brisbane, 4029, Australia.
Jing X Jing Xiaoxi X University of Chinese Academy of Sciences, Beijing, China.
Hendriks AEJ Hendriks A Emile J AEJ Department of Pediatrics, University of Cambridge, Cambridge, UK.
Drop SLS Drop Sten L S SLS Division of Endocrinology, Department of Pediatrics, Sophia Children's Hospital, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Ikram MA Ikram M Arfan MA Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Gordon S Gordon Scott S Queensland Institute of Medical Research, Brisbane, 4029, Australia.
Zeng C Zeng Changqing C Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Uitterlinden AG Uitterlinden Andre G AG Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Martin NG Martin Nicholas G NG Queensland Institute of Medical Research, Brisbane, 4029, Australia.
Liu F Liu Fan F University of Chinese Academy of Sciences, Beijing, China. liufan@big.ac.cn.
Kayser M Kayser Manfred M Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. m.kayser@erasmusmc.nl.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Human genetics
ISOABBREVIATION: Hum. Genet.
YEAR: 2017
MONTH: Sep
DAY: 18
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1432-1203
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Genet
COUNTRY: Germany
ISSNLINKING: 0340-6717
NLMUNIQUEID: 7613873
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's