Many sequence variants affecting diversity of adult human height

Abstract

Adult human height is one of the classical complex human traits. We searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European Americans and 1,148 African Americans. We then combined these results with previously published results from the Diabetes Genetics Initiative on 3,024 Scandinavians and tested a selected subset of SNPs in 5,517 Danes. We identified 27 regions of the genome with one or more sequence variants showing significant association with height. The estimated effects per allele of these variants ranged between 0.3 and 0.6 cm and, taken together, they explain around 3.7% of the population variation in height. The genes neighboring the identified loci cluster in biological processes related to skeletal development and mitosis. Association to three previously reported loci are replicated in our analyses, and the strongest association was with SNPs in the ZBTB38 gene.

Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits

“…Similarly, rs62621197 (WEAF 4.2%, beta ¼ À0.139, p ¼ 3.22 3 10 À69 ) resides in ADAMTS10, null mutations in which are implicated in Weill-Marchesani syndrome, characterized by short stature. 57 Previously reported, independent variants associated with height at this locus reside upstream of ADAMTS10 (rs4072910 6 ) and in intronic sequence (rs7249094 55 Example of fine-mapping and annotation at the ADAMTS17 (left) and SSC5D (right) loci for association with height. LocusZoom regional association plot shown in (A) and posterior probability (PP) statistics shown in (B) are from the fine-mapping methods CAVIARBF and PRFScore (only variants with PP > 0.1 in either methods are shown); genome-wide annotation of variants (GWAVA) scores; genomic evolutionary rate profiling (GERP) scores; average GERP (in a 100 bp window around each variant) scores; whether the variant is an eQTL signal; number of cell lines in which the variant overlaps with a DNase footprints (peak calls from ENCODE); number of overlapping transcriptional factor binding sites based on ENCODE and JASPAR ChIP-seq; number of cell lines in which the queried locus overlaps with a DNase hypersensitivity site (ENCODE data, peaks from Ensembl); and Variant Effect Predictor (VEP) genic annotation.…”

“…39,55,56 rs72755233 (weighted effect allele frequency [WEAF] 11.2%, beta ¼ À0.0837, p ¼ 5.42 3 10 À56 ) resides in ADAMTS17 and causes a non-conservative threonine to isoleucine amino acid change in the protease domain of this peptidase. Similarly, rs62621197 (WEAF 4.2%, beta ¼ À0.139, p ¼ 3.22 3 10 À69 ) resides in ADAMTS10, null mutations in which are implicated in Weill-Marchesani syndrome, characterized by short stature.…”

PLAG1 and NCAPG‐LCORL in livestock

“…The region including PLAG1 and some neighboring genes (HSA8q12.1) has been identified as one of the loci for adult human height both in European (Gudbjartsson et al . 2008; Lettre et al . 2008; Lango Allen et al .…”

Predicting human height by Victorian and genomic methods

“…Selection of 54 SNPs used in the study Of the 54 loci influencing human height shown in Supplementary Table 1, 16 were published by Weedon et al, 5 11 by Lettre et al 6 and 27 by Gudbjartsson et al 7 Of the 59 markers reported to be strongly associated with height in these three studies, five were mapped within the same chromosome region. For these loci, we picked up markers with the lowest P-value.…”