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>