@article {6628,
	title = {A systematic mapping approach of 16q12.2/FTO and BMI in more than 20,000 African Americans narrows in on the underlying functional variation: results from the Population Architecture using Genomics and Epidemiology (PAGE) study.},
	journal = {PLoS Genet},
	volume = {9},
	year = {2013},
	month = {2013},
	pages = {e1003171},
	abstract = {<p>Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3 {\texttimes} 10(-6)) had not been highlighted in previous studies. While rs56137030was correlated at r(2)>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations.</p>},
	keywords = {Adaptor Proteins, Signal Transducing, Adult, African Americans, Aged, Aged, 80 and over, Alleles, Body Mass Index, Chromosome Mapping, Continental Population Groups, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Metagenomics, Middle Aged, Obesity, Proteins},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1003171},
	author = {Peters, Ulrike and North, Kari E and Sethupathy, Praveen and Buyske, Steve and Haessler, Jeff and Jiao, Shuo and Fesinmeyer, Megan D and Jackson, Rebecca D and Kuller, Lew H and Rajkovic, Aleksandar and Lim, Unhee and Cheng, Iona and Schumacher, Fred and Wilkens, Lynne and Li, Rongling and Monda, Keri and Ehret, Georg and Nguyen, Khanh-Dung H and Cooper, Richard and Lewis, Cora E and Leppert, Mark and Irvin, Marguerite R and Gu, C Charles and Houston, Denise and B{\r u}zkov{\'a}, Petra and Ritchie, Marylyn and Matise, Tara C and Le Marchand, Lo{\"\i}c and Hindorff, Lucia A and Crawford, Dana C and Haiman, Christopher A and Kooperberg, Charles}
}
@article {6629,
	title = {Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained.},
	journal = {PLoS Genet},
	volume = {9},
	year = {2013},
	month = {2013 Mar},
	pages = {e1003379},
	abstract = {<p>Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1 {\texttimes} 10(-4) in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74\% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies.</p>},
	keywords = {African Americans, Apolipoproteins A, Cholesterol, HDL, Cholesterol, LDL, European Continental Ancestry Group, Genome-Wide Association Study, Humans, Lipoproteins, HDL, Lipoproteins, LDL, Proprotein Convertases, Serine Endopeptidases, Triglycerides},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1003379},
	author = {Wu, Ying and Waite, Lindsay L and Jackson, Anne U and Sheu, Wayne H-H and Buyske, Steven and Absher, Devin and Arnett, Donna K and Boerwinkle, Eric and Bonnycastle, Lori L and Carty, Cara L and Cheng, Iona and Cochran, Barbara and Croteau-Chonka, Damien C and Dumitrescu, Logan and Eaton, Charles B and Franceschini, Nora and Guo, Xiuqing and Henderson, Brian E and Hindorff, Lucia A and Kim, Eric and Kinnunen, Leena and Komulainen, Pirjo and Lee, Wen-Jane and Le Marchand, Lo{\"\i}c and Lin, Yi and Lindstr{\"o}m, Jaana and Lingaas-Holmen, Oddgeir and Mitchell, Sabrina L and Narisu, Narisu and Robinson, Jennifer G and Schumacher, Fred and Stan{\v c}{\'a}kov{\'a}, Alena and Sundvall, Jouko and Sung, Yun-Ju and Swift, Amy J and Wang, Wen-Chang and Wilkens, Lynne and Wilsgaard, Tom and Young, Alicia M and Adair, Linda S and Ballantyne, Christie M and B{\r u}zkov{\'a}, Petra and Chakravarti, Aravinda and Collins, Francis S and Duggan, David and Feranil, Alan B and Ho, Low-Tone and Hung, Yi-Jen and Hunt, Steven C and Hveem, Kristian and Juang, Jyh-Ming J and Kes{\"a}niemi, Antero Y and Kuusisto, Johanna and Laakso, Markku and Lakka, Timo A and Lee, I-Te and Leppert, Mark F and Matise, Tara C and Moilanen, Leena and Nj{\o}lstad, Inger and Peters, Ulrike and Quertermous, Thomas and Rauramaa, Rainer and Rotter, Jerome I and Saramies, Jouko and Tuomilehto, Jaakko and Uusitupa, Matti and Wang, Tzung-Dau and Boehnke, Michael and Haiman, Christopher A and Chen, Yii-der I and Kooperberg, Charles and Assimes, Themistocles L and Crawford, Dana C and Hsiung, Chao A and North, Kari E and Mohlke, Karen L}
}
