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Genome-Wide Analysis Identifies Genetic Effects on Reproductive Success and Ongoing Natural Selection at the Fads Locus Publisher Pubmed



Mathieson I1 ; Day FR2 ; Barban N3 ; Tropf FC4, 5, 6 ; Brazel DM4, 7 ; Van Heemst D47 ; Vaez A8, 9 ; Van Zuydam N10 ; Bitarello BD1 ; Gardner EJ2 ; Akimova ET4, 7 ; Azad A11 ; Bergmann S12, 13, 14 ; Bielak LF15 Show All Authors
Authors
  1. Mathieson I1
  2. Day FR2
  3. Barban N3
  4. Tropf FC4, 5, 6
  5. Brazel DM4, 7
  6. Van Heemst D47
  7. Vaez A8, 9
  8. Van Zuydam N10
  9. Bitarello BD1
  10. Gardner EJ2
  11. Akimova ET4, 7
  12. Azad A11
  13. Bergmann S12, 13, 14
  14. Bielak LF15
  15. Boomsma DI16, 17
  16. Bosak K18
  17. Brumat M19
  18. Buring JE20, 21
  19. Cesarini D22, 23, 24
  20. Chasman DI20, 21
  21. Chavarro JE25, 26, 27
  22. Cocca M28
  23. Concas MP28
  24. Davey Smith G29
  25. Davies G30
  26. Deary IJ30
  27. Esko T31, 32
  28. Faul JD33
  29. Franco O34, 35
  30. Ganna A36, 37
  31. Gaskins AJ38
  32. Gelemanovic A39
  33. De Geus EJC16
  34. Gieger C40
  35. Girotto G19, 28
  36. Gopinath B41
  37. Grabe HJ42
  38. Gunderson EP43
  39. Hayward C44
  40. He C45, 46
  41. Hill WD30
  42. Hoffmann ER11
  43. Homuth G48
  44. Hottenga JJ16
  45. Huang H25
  46. Hyppnen E49, 50
  47. Ikram MA34
  48. Jansen R51
  49. Johannesson M52
  50. Kamali Z8, 9
  51. Kardia SLR15
  52. Kavousi M34
  53. Kifley A41
  54. Kiiskinen T36, 53
  55. Kraft P25, 54
  56. Kuhnel B40
  57. Langenberg C2
  58. Liew G41
  59. Van Der Most PJ8
  60. Lind PA55
  61. Luan J2
  62. Magi R31
  63. Magnusson PKE56
  64. Mahajan A57, 58
  65. Martin NG59
  66. Mbarek H16, 60
  67. Mccarthy MI57, 58
  68. Mcmahon G61
  69. Medland SE55
  70. Meitinger T62
  71. Metspalu A31, 63
  72. Mihailov E31
  73. Milani L31
  74. Missmer SA25, 64, 65
  75. Mitchell P41
  76. Mollegaard S66
  77. Mookkanamori DO67, 68
  78. Morgan A28
  79. De Mutsert R67
  80. Nauck M69
  81. Nolte IM8
  82. Noordam R47
  83. Penninx BWJH70
  84. Peters A71
  85. Peyser PA15
  86. Polasek O39, 72
  87. Power C73
  88. Pribisalic A39
  89. Redmond P30
  90. Richedwards JW25, 27, 74
  91. Ridker PM20, 21
  92. Rietveld CA75, 76
  93. Ring SM29
  94. Rose LM20
  95. Rueedi R12, 13
  96. Shukla V11
  97. Smith JA15, 33
  98. Stankovic S2
  99. Stefansson K77
  100. Stockl D71
  101. Strauch K78, 79, 80
  102. Swertz MA81
  103. Teumer A82
  104. Thorleifsson G77
  105. Thorsteinsdottir U77
  106. Thurik AR75, 76, 83
  107. Timpson NJ29
  108. Turman C25
  109. Uitterlinden AG75, 84
  110. Waldenberger M40, 71
  111. Wareham NJ2
  112. Weir DR33
  113. Willemsen G16
  114. Zhao JH2
  115. Zhao W15
  116. Zhao Y2
  117. Snieder H8
  118. Den Hoed M10
  119. Ong KK2
  120. Mills MC4, 7, 81, 85
  121. Perry JRB2

Source: Nature Human Behaviour Published:2023


Abstract

Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success. © 2023, The Author(s), under exclusive licence to Springer Nature Limited.
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