10.1371/journal.pone.0125660
Anna-Lena Volckmar
Anna-Lena
Volckmar
Jie-Yun Song
Jie-Yun
Song
Ivonne Jarick
Ivonne
Jarick
Carolin Pütter
Carolin
Pütter
Maria Göbel
Maria
Göbel
Lucie Horn
Lucie
Horn
Christoph Struve
Christoph
Struve
Katharina Haas
Katharina
Haas
Nadja Knoll
Nadja
Knoll
Harald Grallert
Harald
Grallert
Thomas Illig
Thomas
Illig
Thomas Reinehr
Thomas
Reinehr
Hai-Jun Wang
Hai-Jun
Wang
Johannes Hebebrand
Johannes
Hebebrand
Anke Hinney
Anke
Hinney
Fine Mapping of a GWAS-Derived Obesity Candidate Region on Chromosome 16p11.2
Public Library of Science
2015
TaqMan SNP Genotyping
APOBR p.Pro 428Ala
association
body mass index
SSCP
GWAS
SH 2B APOBR
polymorphisms rs 180743
controls.MethodsThe coding regions
chromosomal region chr 16p
MB
gene
SULT 1A TUFM
silico analyses
SULT 1A SULT 1A
97 chromosomal loci
TOF
615 obesity trios
SH 2B
variant
MALDI
2015-05-08 13:00:56
Dataset
https://plos.figshare.com/articles/dataset/Fine_Mapping_of_a_GWAS_Derived_Obesity_Candidate_Region_on_Chromosome_16p11_2/2664985
<div><p>Introduction</p><p>Large-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 (<i>SH2B1</i>, <i>APOBR</i>, sulfotransferases: <i>SULT1A1</i> and <i>SULT1A2</i>, <i>TUFM</i>). We had previously described a rare mutation in <i>SH2B1</i> solely identified in extremely obese individuals but not in lean controls.</p><p>Methods</p><p>The coding regions of the genes <i>APOBR</i>, <i>SULT1A1</i>, <i>SULT1A2</i>, and <i>TUFM</i> 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). <i>In silico</i> tools were used for the prediction of potential functional effects of detected variants.</p><p>Results</p><p>Except for <i>TUFM</i> we detected non-synonymous variants in all screened genes. Two polymorphisms rs180743 (<i>APOBR</i> p.Pro428Ala) and rs3833080 (<i>APOBR</i> p.Gly369_Asp370del9) showed nominal association to (extreme) obesity (uncorrected p = 0.003 and p = 0.002, respectively). <i>In silico</i> analyses predicted a functional implication for rs180743 (<i>APOBR</i> p.Pro428Ala). Both <i>APOBR</i> variants are located in the repetitive region with unknown function.</p><p>Conclusion</p><p>Variants in <i>APOBR</i> contributed as strongly as variants in <i>SH2B1</i> to the association with extreme obesity in the chromosomal region chr16p11.2. <i>In silico</i> analyses implied no functional effect of several of the detected variants. Further <i>in vitro</i> or <i>in vivo</i> analyses on the functional implications of the obesity associated variants are warranted.</p></div>