☆ 4.8 Article

Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

NATURE GENETICS (2010)

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Journal

NATURE GENETICS
Volume 42, Issue 12, Pages 1077-U73

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ng.714

Keywords

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Categories

Genetics & Heredity

Funding

  1. Academy of Finland (Finnish Centre of Excellence in Complex Disease Genetics) [129680, 120315, 129287, 129494]
  2. Affymetrix [N02-HL-6-4278]
  3. Agency of Science, Technology and Research of Singapore (A*STAR)
  4. Althingi (the Icelandic Parliament)
  5. American Heart Association [0855082E]
  6. Amgen
  7. Augustinus Foundation
  8. Australian National Health and Medical Research Council [241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498, 619667]
  9. Australian Research Council [A7960034, A79801419, A79906588, DP0212016, DP0343921, DP0770096]
  10. Baltimore Veterans Administration Medical Center Geriatrics Research
  11. Canadian Institutes of Health Research [166067]
  12. Cancer Research United Kingdom
  13. Cariplo Foundation
  14. Center for Disease Control and Prevention (USA), Centre for Medical Systems Biology (CMSB)
  15. Chief Scientist Office of the Scottish Government
  16. Clinical Nutrition Research Unit of Maryland [P30 DK072488]
  17. Danish National Research Foundation
  18. Danish Pharmacists' Fund
  19. Egmont Foundation
  20. Erasmus Medical Center
  21. Erasmus University
  22. Estonian Government [SF0180142s08]
  23. European Commision [212111 BBMRI, 205419 ECOGENE, 201413 ENGAGE, HEALTH-F2-2008-201865-GEFOS, HEALTH-F2-2008-35627, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550 HYPERGENES, 245536 OPENGENE, TREAT-OA, QLG2-CT-2002-01254, EU/QLRT-2001-01254, ERC-230374]
  24. European Union [LSHG-CT-2006-018947, LSHM-CT-2003-503041]
  25. European Regional Development Fund
  26. Faculty of Biology and Medicine of Lausanne, Switzerland
  27. Fondazione Compagnia di San Paolo Health Ministry, Framingham Heart Study [N01-HC-25195]
  28. GENEVA Coordinating Center [U01HG004446]
  29. German Federal Ministry of Education and Research
  30. German National Genome Research Network [NGFN-2, 01GS0823]
  31. Giorgi-Cavaglieri Foundation
  32. GlaxoSmithKline
  33. Health Fund of the Danish Health Insurance Societies
  34. Helmholtz Zentrum Munchen-German Research Center for Environmental Health
  35. Hjartavernd (the Icelandic Heart Association)
  36. Italian Ministry of Health [ICS110.1/RF97.71, RF-FSR-2007-647201]
  37. Juvenile Diabetes Research Foundation International (JDRF)
  38. Leenaards Foundation
  39. March of Dimes Birth Defects Foundation
  40. Medical Research Council [G0000934, G0500539, G0701863]
  41. National Cancer Institute [CA40356, CA98233, P01CA087969, P01CA055075, CA047988, CA63464, CA54281, CA136792, CA089392, CA104021]
  42. Munich Center of Health Sciences (MC Health, LMUinnovativ)
  43. National Health and Medical Research Council of Australia [572613, 003209]
  44. National Heart, Lung, and Blood Institute [HL043851, HL087679, HL69757, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, RC2 HL102419]
  45. National Human Genome Research Institute (NHGRI)
  46. National Institute of Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002, AG-16592, R21AG032598]
  47. National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute on Aging ((NIAMS/NIA) [R01 AR/AG 41398)]
  48. National Institute of Child Health and Human Development [HD-061437]
  49. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK058845, U01 DK062418]
  50. National Institute on Alcohol Abuse and Alcoholism (NIAAA)
  51. National Institute of Allergy and Infectious Diseases (NIAID)
  52. National Institute on Drug Abuse (NIDA)
  53. National Institutes of Health [U01HG004446, AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, HHSN268200782096C, M01 RR-00750, MH66206, N01-AG-12100, N01-AG-1-2109, P01-AG-18397, R01-088119, R01-DA013423, RFAHG006033, U01DE018993, U01DE018903, U01HG004422, U01HL72515, U01 HL84756, U01HG004399, U01HG004402, U01HG004415, U01HG004423, U01HG004436, U01HG004438, U01HG004726, U01HG004728, U01HG004729, U01HG004735, U01HG004738, U01HG04424, U10AA008401, U54RR025204-01, UL1RR025005, UL1 RR025774, Z01CP010200, HHSN268200625226C]
  54. National Institute for Health Research Cambridge Biomedical Research Centre
  55. Netherlands Organization for Scientific Research [904-61-193, 575-25-006, 480-04-004, 56-464-14192, NWO 480-05-003, 175.010.2005.011, 911-03-012, 014-93-015]
  56. Netherlands Genomic Initiative (NGI) [050-060-810]
  57. National Institute on Aging (NIA)
  58. Laboratory of Neurogenetics
  59. US National Institutes of Health Genes, Environment and Health Initiative
  60. Republic of Croatia Ministry of Science, Education and Sports [108-1080315-0302]
  61. Robert Dawson Evans Endowment
  62. Royal Society, Royal Swedish Academy of Science
  63. State of Bavaria, Germany
  64. Susan G. Komen Breast Cancer Foundation
  65. Swedish Foundation for Strategic Research (SSF)
  66. Swedish Heart-Lung Foundation
  67. Swedish Ministry of Higher Education and Research
  68. Swedish Research Council
  69. Swedish Society of Medicine
  70. Swiss National Science Foundation [33CSCO-122661, 3100AO-116323/1]
  71. University of Bristol, University of Maryland General Clinical Research Center [M01 RR 16500]
  72. Wellcome Trust [068545/Z/02, 076467/Z/05/Z, 077016/Z/05/Z, 89061/Z/09/Z, 079895]
  73. Western Australian DNA Bank
  74. Western Australian Genetic Epidemiology Resource
  75. MRC [MC_U106179472, MC_U106188470, MC_U127561128, G0000934, G0701863, G0600705] Funding Source: UKRI
  76. Cancer Research UK [10118, 11022] Funding Source: researchfish
  77. Cancer Research UK
  78. The Francis Crick Institute [10124] Funding Source: researchfish
  79. Chief Scientist Office [CZB/4/710] Funding Source: researchfish
  80. Medical Research Council [G9815508, MC_U106179471, MC_U127561128, MC_U106179472, G0600705, G0401527, MC_U106188470, G0000934, G0801056B, G0701863] Funding Source: researchfish

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To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 x 10(-60)) and 9q31.2 (P = 2.2 x 10(-33)), we identified 30 new menarche loci (all P < 5 x 10(-8)) and found suggestive evidence for a further 10 loci (P < 1.9 x 10(-6)). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

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