title: The future for genetic studies in reproduction.
abstract: Genetic factors contribute to risk of many common diseases affecting reproduction and fertility. In recent years, methods for genome-wide association studies (GWAS) have revolutionized gene discovery for common traits and diseases. Results of GWAS are documented in the Catalog of Published Genome-Wide Association Studies at the National Human Genome Research Institute and report over 70 publications for 32 traits and diseases associated with reproduction. These include endometriosis, uterine fibroids, age at menarche and age at menopause. Results that pass appropriate stringent levels of significance are generally well replicated in independent studies. Examples of genetic variation affecting twinning rate, infertility, endometriosis and age at menarche demonstrate that the spectrum of disease-related variants for reproductive traits is similar to most other common diseases. GWAS 'hits' provide novel insights into biological pathways and the translational value of these studies lies in discovery of novel gene targets for biomarkers, drug development and greater understanding of environmental factors contributing to disease risk. Results also show that genetic data can help define sub-types of disease and co-morbidity with other traits and diseases. To date, many studies on reproductive traits have used relatively small samples. Future genetic marker studies in large samples with detailed phenotypic and clinical information will yield new insights into disease risk, disease classification and co-morbidity for many diseases associated with reproduction and infertility.
authors: Department of Genetics and Computational Biology, Queensland Institute of Medical Research, Brisbane, Australia.
authors: G W
authors: GW
authors: Montgomery
authors: K T
authors: KT
authors: Zondervan
authors: D R
authors: DR
authors: Nyholt
mesh_terms: D004715:Endometriosis / Q000235:genetics; D005260:Female; D005298:Fertility / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D007889:Leiomyoma / Q000235:genetics; D008572:Menarche / Q000235:genetics; D008593:Menopause / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012098:Reproduction / Q000235:genetics*
keywords: GWAS; gene discovery; reproductive traits; review; translation
references: Pharmacogenomics. 2009 Feb;10(2):181-90
references: 19207019
references: J Med Genet. 2013 Jan;50(1):43-6
references: 23142796
references: Am J Epidemiol. 2013 Aug 1;178(3):451-60
references: 23558354
references: Nature. 2005 Oct 27;437(7063):1299-320
references: 16255080
references: Nat Rev Genet. 2013 Aug;14(8):549-58
references: 23835440
references: Annu Rev Genomics Hum Genet. 2009;10:387-406
references: 19715440
references: Twin Res. 2004 Dec;7(6):548-55
references: 15607004
references: Nat Genet. 2008 Jul;40(7):838-40
references: 18488026
references: Hum Mol Genet. 2013 Apr 1;22(7):1465-72
references: 23307926
references: Am J Hum Genet. 2012 Jan 13;90(1):7-24
references: 22243964
references: Gut. 2008 Jun;57(6):717-20
references: 18272545
references: Fertil Steril. 2012 May;97(5):1143-51.e1-3
references: 22424617
references: Fertil Steril. 1999 Apr;71(4):701-10
references: 10202882
references: Hum Reprod. 2002 Jun;17(6):1415-23
references: 12042253
references: N Engl J Med. 2010 Jul 8;363(2):166-76
references: 20647212
references: Nat Genet. 2013 Oct;45(10):1238-1243
references: 24013639
references: Am J Epidemiol. 2012 Dec 15;176(12):1159-68
references: 23161897
references: Hum Mol Genet. 2013 Jul 1;22(13):2735-47
references: 23449627
references: Nat Genet. 2011 Oct 09;43(11):1066-73
references: 21983784
references: Mol Cell Endocrinol. 2013 May 6;370(1-2):138-48
references: 23499866
references: Nat Genet. 2012 Jul 22;44(8):955-9
references: 22820512
references: Nat Genet. 2009 Jun;41(6):648-50
references: 19448620
references: Am J Hum Genet. 2010 May 14;86(5):773-82
references: 20398887
references: Curr Obstet Gynecol Rep. 2012 Sep;1(3):124-137
references: 22924156
references: Science. 2002 Jun 21;296(5576):2225-9
references: 12029063
references: Nat Genet. 2009 Jun;41(6):724-8
references: 19448621
references: Curr Opin Psychiatry. 2012 Mar;25(2):83-8
references: 22249081
references: J Hum Genet. 2010 Dec;55(12):816-21
references: 20844546
references: Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7
references: 19474294
references: Nat Rev Genet. 2006 May;7(5):385-94
references: 16619052
references: Am J Hum Genet. 2012 Oct 5;91(4):621-8
references: 23040493
references: Fertil Steril. 2013 Mar 1;99(3):768-776.e1
references: 23199610
references: PLoS Genet. 2013 Mar;9(3):e1003348
references: 23555274
references: Genet Epidemiol. 2008 Apr;32(3):227-34
references: 18300295
references: Nat Genet. 2013 Feb;45(2):197-201
references: 23263489
references: Nat Genet. 2012 Dec;44(12):1355-9
references: 23104006
references: Hum Reprod Update. 2008 Sep-Oct;14(5):447-57
references: 18535005
references: Georgian Med News. 2006 May;(134):55-8
references: 16783066
references: Nat Genet. 2009 Jun;41(6):734-8
references: 19448622
references: Nat Genet. 2012 Jan 22;44(3):260-8
references: 22267201
references: Fertil Steril. 1981 Oct;36(4):433-45
references: 7026295
references: Nat Genet. 2008 Aug;40(8):955-62
references: 18587394
references: Nat Genet. 2011 May;43(5):447-50
references: 21460842
references: Nat Genet. 2010 Aug;42(8):707-10
references: 20601957
references: Curr Diab Rep. 2010 Dec;10(6):485-97
references: 20886378
references: Nature. 2012 Sep 6;489(7414):57-74
references: 22955616
references: Nat Genet. 2007 May;39(5):596-604
references: 17435756
references: J Am Acad Dermatol. 2012 Jul;67(1):139-47
references: 22305044
references: Nat Genet. 2003 Mar;33 Suppl:228-37
references: 12610532
references: Best Pract Res Clin Endocrinol Metab. 2012 Apr;26(2):119-32
references: 22498243
references: PLoS One. 2013;8(3):e58257
references: 23472165
references: Hum Reprod. 2001 Oct;16(10):2050-5
references: 11574490
references: N Engl J Med. 2012 Dec 20;367(25):2370-1
references: 23252523
references: Hum Reprod Update. 2001 Jan-Feb;7(1):8-14
references: 11212080
references: Cell. 2010 Jun 25;141(7):1135-45
references: 20602997
references: Nat Genet. 2011 Jan;43(1):51-4
references: 21151130
references: Nat Genet. 2001 Oct;29(2):229-32
references: 11586305
references: Nat Genet. 2009 Jun;41(6):729-33
references: 19448623
references: Genetics. 2011 Feb;187(2):367-83
references: 21115973
references: Nature. 2007 Oct 18;449(7164):851-61
references: 17943122
references: Nat Genet. 2010 Dec;42(12):1077-85
references: 21102462
references: J Clin Endocrinol Metab. 2006 Nov;91(11):4713-6
references: 16954162
references: Nature. 2011 Nov 13;480(7375):99-103
references: 22080950
references: Hum Mol Genet. 2013 Feb 15;22(4):832-41
references: 23193196
references: Nature. 2010 Oct 14;467(7317):832-8
references: 20881960
references: Environ Health Perspect. 2010 Sep;118(9):1280-5
references: 20423815
references: Philos Trans R Soc Lond B Biol Sci. 2005 Jul 29;360(1459):1387-93
references: 16048782
references: Mol Cell Endocrinol. 2014 Jan 25;382(1):767-779
references: 22613007
references: Am J Hum Genet. 2013 Feb 7;92(2):197-209
references: 23375658
references: Hum Hered. 2012;73(1):18-25
references: 22212296
references: Fertil Steril. 2006 Mar;85(3):775-9
references: 16500362
references: Trends Endocrinol Metab. 2004 Oct;15(8):356-61
references: 15380806
references: Nat Genet. 2010 Dec;42(12):1118-25
references: 21102463
references: Nat Genet. 2002 Sep;32(1):135-42
references: 12161752
references: Nat Genet. 2008 May;40(5):609-15
references: 18391951
references: Nat Biotechnol. 2012 Apr 10;30(4):317-20
references: 22491277
references: Reproduction. 2004 Oct;128(4):379-86
references: 15454632
references: Nat Genet. 2012 Jan 22;44(3):312-8
references: 22267197
references: Hum Reprod. 2013 Mar;28(3):835-9
references: 23315067
references: PLoS Genet. 2009 Mar;5(3):e1000420
references: 19282985
references: Nat Genet. 2009 Jun;41(6):645-7
references: 19448619
references: Transl Res. 2012 Feb;159(2):64-79
references: 22243791