138. GENOME-WIDE LINKAGE SCAN FOR FAMILIAL DIZYGOTIC TWINNING
J. N. Painter A , G. Willemsen B , D. R. Nyholt A , C. Hoekstra B , D. Duffy A , A. Henders A , L. Wallace A , S. Healy A , L. A. Cannon-Albright C , M. Skolnick C , N. G. Martin A , D. I. Boomsma B and G. W. Montgomery AA Molecular Epidemiology, Queensland Institute of Medical Research, Herston, QLD, Australia.
B Department of Biological Psychology, VU University, Amsterdam, Netherlands.
C Department of Internal Medicine, University of Utah, Salt Lake City, United States.
Reproduction, Fertility and Development 22(9) 56-56 https://doi.org/10.1071/SRB10Abs138
Published: 6 September 2010
Abstract
The tendency to conceive dizygotic (DZ) twins is a complex trait influenced by genetic and environmental factors. To search for new candidate loci for twinning we have conducted a genome-wide linkage scan in 525 families using microsatellite and single nucleotide polymorphism (SNP) marker panels. Non-parametric linkage analyses including 523 families containing a total of 1115 mothers of DZ twins (MODZT) from Australia and New Zealand (ANZ) and The Netherlands (NL) produced four linkage peaks above the threshold for suggestive linkage, including a highly suggestive peak at the extreme telomeric end of chromosome 6 with an exponential (exp)LOD score of 2.813 (P = 0.0002). Since the DZ twinning rate increases steeply with maternal age independent of genetic effects, we also investigated linkage including only families where at least one MODZT gave birth to her first set of twins before the age of 30. These analyses produced a maximum expLOD score of 2.718 (p = 0.0002), largely due to linkage signal from the ANZ cohort, however, ordered subset analyses indicated this result is most likely a chance finding in the combined dataset. Linkage analyses were also performed for two large DZ twinning families from the USA, one of which produced a peak on chromosome 2 in the region of two potential candidate genes. Sequencing of FSHR and FIGLA, along with INHBB in MODZTs from two large NL families with family-specific linkage peaks directly over this gene, revealed a potentially functional variant in the 5’ untranslated region of FSHR that segregated with the DZ twinning phenotype in the UT family. Work is continuing screening candidate genes. Our data provide further evidence for complex inheritance of familial DZ twinning.
