title: A genome wide linkage scan for dizygotic twinning in 525 families of mothers of dizygotic twins.
abstract: BACKGROUND
  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 conducted a genome-wide linkage scan in 525 families using microsatellite and single nucleotide polymorphism marker panels.
  
  
  RESULTS
  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 logarithm of odds [(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 Utah family.
  
  
  CONCLUSIONS
  Our data provide further evidence for complex inheritance of familial DZ twinning.
authors.affiliation: Molecular Epidemiology, Genetic Epidemiology and Neurogenetics Laboratories, Queensland Institute of Medical Research, Brisbane, Australia. jodie.painter@qimr.edu.au
authors.forename: Jodie N
authors.initials: JN
authors.lastname: Painter
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.forename: Dale
authors.initials: D
authors.lastname: Nyholt
authors.forename: Chantal
authors.initials: C
authors.lastname: Hoekstra
authors.forename: David L
authors.initials: DL
authors.lastname: Duffy
authors.forename: Anjali K
authors.initials: AK
authors.lastname: Henders
authors.forename: Leanne
authors.initials: L
authors.lastname: Wallace
authors.forename: Sue
authors.initials: S
authors.lastname: Healey
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cannon-Albright
authors.forename: Mark
authors.initials: M
authors.lastname: Skolnick
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
mesh_terms: D001315:Australia; D005190:Family; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008423:Maternal Age; D009426:Netherlands; D009520:New Zealand; D010641:Phenotype; D014429:Twins, Dizygotic / Q000235:genetics*