Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations

被引：15

作者：

Yoneyama, S. ^{[1
]}

Yao, J. ^{[2
]}

Guo, X. ^{[2
]}

Fernandez-Rhodes, L. ^{[1
]}

Lim, U. ^{[3
]}

Boston, J. ^{[4
]}

Buzkova, P. ^{[5
]}

Carlson, C. S. ^{[6
]}

Cheng, I. ^{[7
]}

Cochran, B. ^{[8
,9
]}

Cooper, R. ^{[10
]}

Ehret, G. ^{[11
]}

Fornage, M. ^{[12
,13
]}

Gong, J. ^{[6
]}

Gross, M. ^{[14
]}

Gu, C. C. ^{[15
]}

Haessler, J. ^{[6
]}

Haiman, C. A. ^{[16
]}

Henderson, B. ^{[16
]}

Hindorff, L. A. ^{[17
]}

Houston, D. ^{[18
]}

Irvin, M. R. ^{[19
]}

Jackson, R. ^{[20
]}

Kuller, L. ^{[21
]}

Leppert, M. ^{[22
]}

Lewis, C. E. ^{[23
]}

Li, R. ^{[17
]}

Le Marchand, L. ^{[3
]}

Matise, T. C. ^{[24
]}

Nguyen, K-D H. ^{[11
]}

Chakravarti, A. ^{[11
]}

Pankow, J. S. ^{[25
]}

Pankratz, N. ^{[14
]}

Pooler, L. ^{[16
]}

Ritchie, M. D. ^{[26
]}

Bien, S. A. ^{[6
]}

Wassel, C. L. ^{[27
]}

Chen, Y-D I. ^{[2
]}

Taylor, K. D. ^{[2
]}

Allison, M. ^{[28
]}

Rotter, J. I. ^{[2
]}

Schreiner, P. J.

Schumacher, F. ^{[16
]}

Wilkens, L. ^{[3
]}

Boerwinkle, E. ^{[29
,30
,31
]}

Kooperberg, C. ^{[6
]}

Peters, U. ^{[6
]}

Buyske, S. ^{[24
]}

Graff, M. ^{[1
]}

North, K. E. ^{[1
,32
]}

机构：

[1] Univ N Carolina, Dept Epidemiol, 137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA

[2] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, LABioMed, Torrance, CA 90509 USA

[3] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA

[4] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA

[5] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[6] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA

[7] Canc Prevent Inst Calif, Fremont, CA USA

[8] Baylor Coll Med, Houston, TX 77030 USA

[9] Univ Hosp Geneva, Div Cardiol, Geneva, Switzerland

[10] Loyola Univ, Dept Publ Hlth, Chicago, IL 60611 USA

[11] Johns Hopkins Univ, Sch Med, Ctr Complex Dis Genom, McKusick Nathans Inst Genet Med, Baltimore, MD USA

[12] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA

[13] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA

[14] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA

[15] Washington Univ, Dept Biostat, St Louis, MO USA

[16] Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA USA

[17] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA

[18] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA

[19] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA

[20] Ohio State Med Ctr, Dept Internal Med, Columbus, OH USA

[21] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA

[22] Univ Utah, Dept Human Genet, Salt Lake City, UT USA

[23] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA

[24] Rutgers State Univ, Dept Genet, Piscataway, NJ USA

[25] Univ Minnesota, Sch Publ Hlth, Dept Epidemiol & Community Hlth, Minneapolis, MN USA

[26] Penn State Univ, Dept Biochem & Mol Biol, State Coll, PA USA

[27] Univ Vermont, Dept Pathol & Lab Med, Coll Med, Colchester, VT USA

[28] Univ Calif San Diego, Sch Med, Dept Prevent Med, San Diego, CA 92103 USA

[29] Ctr Human Genet, Houston, TX USA

[30] Inst Mol Med, Houston, TX USA

[31] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA

[32] Carolina Ctr Genome Sci, Chapel Hill, NC USA

来源：

INTERNATIONAL JOURNAL OF OBESITY | 2017年 / 41卷 / 02期

关键词：

GENOME-WIDE ASSOCIATION; BODY-FAT DISTRIBUTION; TO-HIP RATIO; WAIST CIRCUMFERENCE; SEX-DIFFERENCES; COMPLEX TRAITS; UNITED-STATES; MASS INDEX; ADULTS; LOCI;

D O I：

10.1038/ijo.2016.207

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 arraywide 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 sexcombined 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.

引用

页码：324 / 331

页数：8

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