Variation in bone morphogenetic protein 15 is not associated with spontaneous human dizygotic twinning.
BACKGROUND
Spontaneous dizygotic (DZ) twinning in humans is under genetic control. In sheep, heterozygous loss of function mutations in bone morphogenetic protein 15 (BMP15) increase ovulation and hence twinning rates.


METHODS
To investigate the role of BMP15 in human twinning, we typed 14 common variants, 4 rare novel variants initially detected by sequencing 279 mothers of DZ twins (MODZT) and 17 variants previously associated with premature ovarian failure (POF) in 933 DZ twinning families. We also typed five additional POF associated GDF9 variants.


RESULTS
There was some evidence for association between DZ twinning and a common intronic BMP15 variant (rs3897937), but this was not significant after correction for multiple testing. Three of the four novel variants (p.Pro174Ser, p.Ala311Thr and p.Arg392Thr) occurred in 1-5 MODZT but were not detected in 1512 controls. We also detected three POF associated mutations in both BMP15 and GDF9 at low frequencies in MODZT and controls.


CONCLUSIONS
We conclude that neither rare nor common BMP15 variants play a significant role in the variation in human DZ twinning.
Zhao
Zhen Zhen
ZZ
Molecular Epidemiology, Queensland Institute of Medical Research, Royal Brisbane Hospital, Brisbane, QLD, Australia.
Painter
Jodie N
JN
Palmer
James S
JS
Webb
Penelope M
PM
Hayward
Nicholas K
NK
Whiteman
David C
DC
Boomsma
Dorret I
DI
Martin
Nicholas G
NG
Duffy
David L
DL
Montgomery
Grant W
GW
D000483:Alleles; D055430:Bone Morphogenetic Protein 15 / Q000737:chemistry / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014429:Twins, Dizygotic / Q000235:genetics*
C525901:BMP15 protein, human; D055430:Bone Morphogenetic Protein 15