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| PMID |
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| TITLE |
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| Genome-wide compound heterozygote analysis highlights alleles associated with adult height in Europeans. |
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| ABSTRACT |
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| 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. |
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| DATE PUBLISHED |
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| HISTORY |
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| 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 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Zhong K |
|
Zhong |
Kaiyin |
K |
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Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. |
| Zhu G |
|
Zhu |
Gu |
G |
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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 |
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Department of Pediatrics, University of Cambridge, Cambridge, UK. |
| Drop SLS |
|
Drop |
Sten L S |
SLS |
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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 |
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Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. |
| Gordon S |
|
Gordon |
Scott |
S |
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Queensland Institute of Medical Research, Brisbane, 4029, Australia. |
| Zeng C |
|
Zeng |
Changqing |
C |
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Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China. |
| Uitterlinden AG |
|
Uitterlinden |
Andre G |
AG |
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Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
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Queensland Institute of Medical Research, Brisbane, 4029, Australia. |
| Liu F |
|
Liu |
Fan |
F |
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University of Chinese Academy of Sciences, Beijing, China. liufan@big.ac.cn. |
| Kayser M |
|
Kayser |
Manfred |
M |
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Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. m.kayser@erasmusmc.nl. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: Human genetics |
| ISOABBREVIATION: Hum. Genet. |
| YEAR: 2017 |
| MONTH: Sep |
| DAY: 18 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1432-1203 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Hum Genet |
| COUNTRY: Germany |
| ISSNLINKING: 0340-6717 |
| NLMUNIQUEID: 7613873 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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