@article {7599, title = {Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations.}, journal = {Int J Obes (Lond)}, volume = {41}, year = {2017}, month = {2017 Feb}, pages = {324-331}, abstract = {

BACKGROUND/OBJECTIVES: Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition.

SUBJECTS/METHODS: To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine-mapping cardiovascular-associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants.

RESULTS: Of the 17 WHR loci, eight single-nucleotide polymorphisms (SNPs) located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40\% drop in number of putative SNPs and 20\% drop in genomic region). Similar to previous studies, the significant SNPs in the female-stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses.

CONCLUSIONS: Of 17 previously identified loci, four loci replicated in the African ancestry populations of this study. Utilizing different linkage disequilibrium patterns observed between European and African ancestries, we narrowed the suggestive region containing causative variants for all four loci.

}, issn = {1476-5497}, doi = {10.1038/ijo.2016.207}, author = {Yoneyama, S and Yao, J and Guo, X and Fernandez-Rhodes, L and Lim, U and Boston, J and B{\r u}{\v z}kov{\'a}, P and Carlson, C S and Cheng, I and Cochran, B and Cooper, R and Ehret, G and Fornage, M and Gong, J and Gross, M and Gu, C C and Haessler, J and Haiman, C A and Henderson, B and Hindorff, L A and Houston, D and Irvin, M R and Jackson, R and Kuller, L and Leppert, M and Lewis, C E and Li, R and Le Marchand, L and Matise, T C and Nguyen, K-Dh and Chakravarti, A and Pankow, J S and Pankratz, N and Pooler, L and Ritchie, M D and Bien, S A and Wassel, C L and Chen, Y-DI and Taylor, K D and Allison, M and Rotter, J I and Schreiner, P J and Schumacher, F and Wilkens, L and Boerwinkle, E and Kooperberg, C and Peters, U and Buyske, S and Graff, M and North, K E} } @article {7679, title = {Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI.}, journal = {Int J Obes (Lond)}, volume = {42}, year = {2018}, month = {2018 Mar}, pages = {384-390}, abstract = {

OBJECTIVE: Body mass index (BMI) is commonly used to assess obesity, which is associated with numerous diseases and negative health outcomes. BMI has been shown to be a heritable, polygenic trait, with close to 100 loci previously identified and replicated in multiple populations. We aim to replicate known BMI loci and identify novel associations in a trans-ethnic study population.

SUBJECTS: Using eligible participants from the Population Architecture using Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans and European Americans. Participants were genotyped on over 200 000 SNPs on the Illumina Metabochip custom array, or imputed into the 1000 Genomes Project (Phase I). Linear regression of the natural log of BMI, adjusting for age, sex, study site (if applicable), and ancestry principal components, was conducted for each race/ethnicity within each study cohort. Race/ethnicity-specific, and combined meta-analyses used fixed-effects models.

RESULTS: We replicated 15 of 21 BMI loci included on the Metabochip, and identified two novel BMI loci at 1q41 (rs2820436) and 2q31.1 (rs10930502) at the Metabochip-wide significance threshold (P<2.5 {\texttimes} 10). Bioinformatic functional investigation of SNPs at these loci suggests a possible impact on pathways that regulate metabolism and adipose tissue.

CONCLUSION: Conducting studies in genetically diverse populations continues to be a valuable strategy for replicating known loci and uncovering novel BMI associations.

}, issn = {1476-5497}, doi = {10.1038/ijo.2017.304}, author = {Gong, J and Nishimura, K K and Fernandez-Rhodes, L and Haessler, J and Bien, S and Graff, M and Lim, U and Lu, Y and Gross, M and Fornage, M and Yoneyama, S and Isasi, C R and B{\r u}{\v z}kov{\'a}, P and Daviglus, M and Lin, D-Y and Tao, R and Goodloe, R and Bush, W S and Farber-Eger, E and Boston, J and Dilks, H H and Ehret, G and Gu, C C and Lewis, C E and Nguyen, K-D H and Cooper, R and Leppert, M and Irvin, M R and Bottinger, E P and Wilkens, L R and Haiman, C A and Park, L and Monroe, K R and Cheng, I and Stram, D O and Carlson, C S and Jackson, R and Kuller, L and Houston, D and Kooperberg, C and Buyske, S and Hindorff, L A and Crawford, D C and Loos, R J F and Le Marchand, L and Matise, T C and North, K E and Peters, U} }