Meta-Analysis of Genome-Wide Scans for Human Adult Stature Identifies Novel Loci and Associations with Measures of Skeletal Frame Size
نویسندگان
چکیده
Recent genome-wide (GW) scans have identified several independent loci affecting human stature, but their contribution through the different skeletal components of height is still poorly understood. We carried out a genome-wide scan in 12,611 participants, followed by replication in an additional 7,187 individuals, and identified 17 genomic regions with GW-significant association with height. Of these, two are entirely novel (rs11809207 in CATSPER4, combined P-value = 6.1x10(-8) and rs910316 in TMED10, P-value = 1.4x10(-7)) and two had previously been described with weak statistical support (rs10472828 in NPR3, P-value = 3x10(-7) and rs849141 in JAZF1, P-value = 3.2x10(-11)). One locus (rs1182188 at GNA12) identifies the first height eQTL. We also assessed the contribution of height loci to the upper- (trunk) and lower-body (hip axis and femur) skeletal components of height. We find evidence for several loci associated with trunk length (including rs6570507 in GPR126, P-value = 4x10(-5) and rs6817306 in LCORL, P-value = 4x10(-4)), hip axis length (including rs6830062 at LCORL, P-value = 4.8x10(-4) and rs4911494 at UQCC, P-value = 1.9x10(-4)), and femur length (including rs710841 at PRKG2, P-value = 2.4x10(-5) and rs10946808 at HIST1H1D, P-value = 6.4x10(-6)). Finally, we used conditional analyses to explore a possible differential contribution of the height loci to these different skeletal size measurements. In addition to validating four novel loci controlling adult stature, our study represents the first effort to assess the contribution of genetic loci to three skeletal components of height. Further statistical tests in larger numbers of individuals will be required to verify if the height loci affect height preferentially through these subcomponents of height.
منابع مشابه
Unveiling the genetic loci for a panicle developmental trait using genome-wide association study in rice
Panicle size has a high correlation with grain yield in rice. There is a bottleneck to identify the additional quantitative trait loci (QTL) for panicle size due to the conventional traits used for QTL mapping. To identify more genetic loci for panicle size, a panicle developmental trait (LNTB, the length from panicle neck-knot to the first primary branch in the rachis) related to panicle size ...
متن کاملNovel genetic loci underlying human intracranial volume identified through genome-wide association
Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also ass...
متن کاملA male-specific quantitative trait locus on 1p21 controlling human stature.
BACKGROUND Many genome-wide scans aimed at complex traits have been statistically underpowered due to small sample size. Combining data from several genome-wide screens with comparable quantitative phenotype data should improve statistical power for the localisation of genomic regions contributing to these traits. OBJECTIVE To perform a genome-wide screen for loci affecting adult stature by c...
متن کاملGenome-wide Association Study to Identify Genes and Biological Pathways Associated with Type Traits in Cattle using Pathway Analysis
Extended Abstract Introduction and Objective: Type traits describing the skeletal characteristics of an animal are moderately to strongly genetically correlate with other economically important traits in cattle including fertility, longevity and carcass traits. The present study aimed to conduct a genome wide association studies (GWAS) based on gene-set enrichment analysis for identifying the ...
متن کاملSynthesizing genome-wide association studies and expression microarray reveals novel genes that act in the human growth plate to modulate height.
Previous meta-analysis of genome-wide association (GWA) studies has identified 180 loci that influence adult height. However, each GWA locus typically comprises a set of contiguous genes, only one of which presumably modulates height. We reasoned that many of the causative genes within these loci influence height because they are expressed in and function in the growth plate, a cartilaginous st...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 5 شماره
صفحات -
تاریخ انتشار 2009