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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.

TitleGenome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
Publication TypeJournal Article
Year of Publication2013
AuthorsBerndt SI, Gustafsson S, Mägi R, et al.
Secondary AuthorsIngelsson E
JournalNat Genet
Volume45
Issue5
Pagination501-12
Date Published2013 May
ISSN1546-1718
KeywordsAnthropometry, Body Height, Body Mass Index, Case-Control Studies, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Meta-Analysis as Topic, Obesity, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Waist-Hip Ratio
Abstract

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

DOI10.1038/ng.2606
Alternate JournalNat Genet
PubMed ID23563607
PubMed Central IDPMC3973018
Grant ListR01 DK093757 / DK / NIDDK NIH HHS / United States
R01 CA082659 / CA / NCI NIH HHS / United States
CZB/4/710 / / Chief Scientist Office / United Kingdom
G9521010 / / Medical Research Council / United Kingdom
098017 / / Wellcome Trust / United Kingdom
RP-PG-0310-1002 / / Department of Health / United Kingdom
K05 AA017688 / AA / NIAAA NIH HHS / United States
U01 HG007416 / HG / NHGRI NIH HHS / United States
T32 GM074905 / GM / NIGMS NIH HHS / United States
R01 DK072193 / DK / NIDDK NIH HHS / United States
G1000143 / / Medical Research Council / United Kingdom
R01 DK075787 / DK / NIDDK NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
MC_U106179471 / / Medical Research Council / United Kingdom
097117 / / Wellcome Trust / United Kingdom
MC_UU_12015/2 / / Medical Research Council / United Kingdom
MC_U123092720 / / Medical Research Council / United Kingdom
14136 / / Cancer Research UK / United Kingdom
MC_U106179472 / / Medical Research Council / United Kingdom
G1002084 / / Medical Research Council / United Kingdom
G0401527 / / Medical Research Council / United Kingdom
090532 / / Wellcome Trust / United Kingdom
MC_PC_U127561128 / / Medical Research Council / United Kingdom
MR/K006584/1 / / Medical Research Council / United Kingdom
P30 DK020572 / DK / NIDDK NIH HHS / United States
R01 HL117626 / HL / NHLBI NIH HHS / United States
MC_U106188470 / / Medical Research Council / United Kingdom
G0601261 / / Medical Research Council / United Kingdom
G0600237 / / Medical Research Council / United Kingdom
MC_U105260558 / / Medical Research Council / United Kingdom