Evidence mapPaperPMID 25955518Full record

ArticlePloS one2015

Fine Mapping of a GWAS-Derived Obesity Candidate Region on Chromosome 16p11.2.

Anna-Lena Volckmar, Jie-Yun Song, Ivonne Jarick, Carolin Pütter, Maria Göbel, Lucie Horn, Christoph Struve, Katharina Haas, Nadja Knoll, Harald Grallert and 5 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 2 pooled it
0.5field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 2 syntheses or guidelines pooled it, 13 citations in OpenAlex.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 2 countries.

Anna-Lena VolckmarDepartment of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Jie-Yun SongInstitute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China.
Ivonne JarickInstitute of Medical Biometry and Epidemiology, University of Marburg, Marburg, Germany.
Carolin PütterInstitute for Human Genetics, Hannover Medical School, Hannover, Germany.
Maria GöbelDepartment of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Lucie HornDepartment of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Christoph StruveDepartment of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Katharina HaasDepartment of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Nadja KnollDepartment of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Harald GrallertInstitute of Epidemiology, Helmholtz-Zentrum Munich, Munich, Germany.
Thomas IlligInstitute of Epidemiology, Helmholtz-Zentrum Munich, Munich, Germany; Hannover Unified Biobank, Hannover Medical School, Hannover, Germany; Institute for Human Genetics, Hannover Medical School, Hannover, Germany.
Thomas ReinehrVestische Hospital for Clinic of Children and Adolescents Medicine, Datteln, University of Witten/Herdecke, Witten, Germany.
Hai-Jun WangInstitute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China.
Johannes HebebrandDepartment of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Anke HinneyDepartment of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
University of Duisburg-Essen · DEMedizinische Hochschule Hannover · DEPeking University · CNHelmholtz Zentrum München · DEPhilipps University of Marburg · DEWitten/Herdecke University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionLarge-scale genome-wide association studies (GWASs) have identified 97 chromosomal loci associated with increased body mass index in population-based studies on adults. One of these SNPs, rs7359397, tags a large region (approx. 1MB) with high linkage disequilibrium (r2>0.7), which comprises five genes (SH2B1, APOBR, sulfotransferases: SULT1A1 and SULT1A2, TUFM). We had previously described a rare mutation in SH2B1 solely identified in extremely obese individuals but not in lean controls.

methodsThe coding regions of the genes APOBR, SULT1A1, SULT1A2, and TUFM were screened for mutations (dHPLC, SSCP, Sanger re-sequencing) in 95 extremely obese children and adolescents. Detected non-synonymous variants were genotyped (TaqMan SNP Genotyping, MALDI TOF, PCR-RFLP) in independent large study groups (up to 3,210 extremely obese/overweight cases, 485 lean controls and 615 obesity trios). In silico tools were used for the prediction of potential functional effects of detected variants.

resultsExcept for TUFM we detected non-synonymous variants in all screened genes. Two polymorphisms rs180743 (APOBR p.Pro428Ala) and rs3833080 (APOBR p.Gly369_Asp370del9) showed nominal association to (extreme) obesity (uncorrected p = 0.003 and p = 0.002, respectively). In silico analyses predicted a functional implication for rs180743 (APOBR p.Pro428Ala). Both APOBR variants are located in the repetitive region with unknown function.

conclusionVariants in APOBR contributed as strongly as variants in SH2B1 to the association with extreme obesity in the chromosomal region chr16p11.2. In silico analyses implied no functional effect of several of the detected variants. Further in vitro or in vivo analyses on the functional implications of the obesity associated variants are warranted.

Indexed as

Chromosomes, Human, Pair 16Genome-Wide Association StudyAdaptor Proteins, Signal TransducingAdolescentAdultArylsulfotransferaseBody Mass IndexChildChromosome MappingFemaleGenotypeHumansLinkage DisequilibriumMaleMiddle AgedMitochondrial ProteinsAdaptor Proteins, Signal Transducingapolipoprotein B receptorArylsulfotransferaseMitochondrial ProteinsPeptide Elongation Factor TuReceptors, LipoproteinSH2B1 protein, humanSULT1A1 protein, humanSULT1A2 protein, humanTUFM protein, human

Identifiers

PMID25955518
PMCPMC4425372
OpenAlexW239401557

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.