4.8 Article

A genome-wide association meta-analysis identifies new childhood obesity loci

Journal

NATURE GENETICS
Volume 44, Issue 5, Pages 526-+

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2247

Keywords

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Funding

  1. MRC [G0400546, G0801056, G0000934, G0600705, G0900554, G0100103, G0601653, G0800582] Funding Source: UKRI
  2. Wellcome Trust [086596/Z/08/Z] Funding Source: Wellcome Trust
  3. British Heart Foundation [PG/09/023/26806] Funding Source: researchfish
  4. Diabetes UK [08/0003775] Funding Source: researchfish
  5. Medical Research Council [G0800582, G0600705, G0600717B, G0801056, G0400546B, G0100103, G0900554, U1475000001, G0400546, G0000934, G0601653, MC_UP_A620_1014, G0801056B] Funding Source: researchfish
  6. National Institute for Health Research [NF-SI-0508-10082, PHCS/C4/4/016] Funding Source: researchfish
  7. British Heart Foundation [PG/09/023/26806, PG/1996183/9569, PG/09/023] Funding Source: Medline
  8. CIHR [MOP-82893] Funding Source: Medline
  9. Diabetes UK [08/0003775] Funding Source: Medline
  10. Medical Research Council [G0601653, G0800582, G0500539, MC_UP_A620_1014, G0600705, G0100103, G0400546, G0000934, G0801056, G0900554, 74882] Funding Source: Medline
  11. NHLBI NIH HHS [5R01HL087679-02, R01 HL061768, 1RC2HL101543, 1RC2HL101651, R01 HL087680, 5R01HL087680, R01 HL076647, RC2 HL101543, R01 HL087679, 5R01HL076647, RC2 HL101651, 5R01HL061768] Funding Source: Medline
  12. NICHD NIH HHS [R01 HD056465-01A1, R01 HD056465-02, R01 HD056465-04, R24 HD050924, R01 HD056465, R01 HD056465-05, R01 HD056465-03] Funding Source: Medline
  13. NIDDK NIH HHS [R01 DK075787, U01 DK062418] Funding Source: Medline
  14. NIEHS NIH HHS [R01 ES014708, R01 ES014447, R01 ES016535, P30 ES007048, 5R03ES014046, P01 ES011627, 5P30ES007048, 5R01ES014708, 5R01ES016535, R03 ES014046, 5R01ES014447, 5P01ES011627, P01 ES009581, 5P01ES009581] Funding Source: Medline
  15. NIMH NIH HHS [R01 MH063706, 1RL1MH083268-01, 5R01MH63706:02, RL1 MH083268] Funding Source: Medline
  16. PHS HHS [R826708-01] Funding Source: Medline
  17. Wellcome Trust [068545/Z/02, 077016/Z/05/Z, 098395, 052515/2/97/2, 090532, WT088431MA, GR069224, 092731, 086596/Z/08/Z, 076467, 083948] Funding Source: Medline
  18. Department of Health [PHCS/C4/4/016] Funding Source: Medline
  19. ORD VA [RD831861-01] Funding Source: Medline

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Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (>= 95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 x 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 x 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 x 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous metaanalysis of adult BMI1.

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