Population structure

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Population structure

• Correlation among subjects
• If this correlation is unaccounted for, then the
  assumptions of independence are violated
• Classic hidden variable problem in statistics

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Linkage disequillibrium

• Multipoint mapping assumes that markers selected
  are in linkage equilibrium
• If markers are associated then the multipoint
  test statistics are affected, and allele sharing
  can be overestimated Huang Q, Shete S, Amos CI
  (2004) Ignoring linkage disequilibrium among
  tightly linked markers induces false-positive
  evidence of linkage for affected sib pair
  analysis. Am J Hum Genet 7511061112

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Association tests when family structure is
deliberate

• Nuclear families
• Sib- ships
• Half sib designs
• Mating designs Diallel, factorial, NC design 2,
  NC design 3
• General pedigree

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Markers associated

• LD between markers can be estimated and taken
  into account
• The Affected-/Discordant-Sib-Pair Design Can
  Guarantee Validity of Multipoint Model-Free
  Linkage Analysis of Incomplete Pedigrees When
  There Is Marker-Marker Disequilibrium Chao Xing,
  Ritwik Sinha, Guan Xing, Qing Lu, and Robert C.
  Elston

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Disequillibrium
B
b
Locus 1
Under independence expected values are the
product of the marginal frequencies
E(pAB)pA.p.B
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Difference between observed and expected values
can be used to test for disquilibrium dABpAB-pA.
p.B
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Dmax the smaller of paB and pAb and Dmin is the
larger of -pAB and pab Dd/Dmax when dD gt 0
and d/Dmin when dlt 0 R2d2/pA.pa.pB.pb