Effects of updating linkage evidence across subsets of data: reanalysis of the autism genetic resource exchange data set.
Results of autism linkage studies have been difficult to interpret across research groups, prompting the use of ever-increasing sample sizes to increase power. However, increasing sample size by pooling disparate collections for a single analysis may, in fact, not increase power in the face of genetic heterogeneity. Here, we applied the posterior probability of linkage (PPL), a method designed specifically to analyze multiple heterogeneous data sets, to the Autism Genetic Resource Exchange collection of families by analyzing six clinically defined subsets of the data and updating the PPL sequentially over the subsets. Our results indicate a substantial probability of linkage to chromosome 1, which had been previously overlooked; our findings also provide a further characterization of the possible parent-of-origin effects at the 17q11 locus that were previously described in this sample. This analysis illustrates that the way in which heterogeneity is addressed in linkage analysis can dramatically affect the overall conclusions of a linkage study.
Bartlett
Christopher W
CW
Center for Statistical Genetics Research, College of Public Health, and Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. christopher-bartlett@uiowa.edu
Goedken
Rhinda
R
Vieland
Veronica J
VJ
D001321:Autistic Disorder / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D002886:Chromosomes, Human, Pair 17; D003627:Data Interpretation, Statistical; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D009679:Nuclear Family
J Neural Transm (Vienna). 2004 Jul;111(7):891-902
15206005
Am J Hum Genet. 2004 May;74(5):1057-63
15065015
Am J Hum Genet. 2002 Jul;71(1):45-55
12048648
Psychol Med. 1999 Jul;29(4):769-86
10473304
Am J Hum Genet. 2002 Jan;70(1):60-71
11741194
Am J Hum Genet. 1999 Aug;65(2):493-507
10417292
Hum Hered. 2001;51(4):199-208
11287741
Hum Hered. 2004;57(2):90-9
15192281
Am J Hum Genet. 2001 Sep;69(3):570-81
11481586
Schizophr Bull. 1987;13(2):261-76
3616518
Am J Hum Genet. 1993 Jan;52(1):210-2
8434589
Am J Hum Genet. 2004 Dec;75(6):1143-8
15486828
Am J Med Genet. 1999 Dec 15;88(6):609-15
10581478
Am J Hum Genet. 2003 Mar;72(3):539-48
12567325
Hum Hered. 2001;51(4):217-25
11287743
Am J Med Genet. 2001 Aug 8;105(6):539-47
11496372
Hum Mol Genet. 1998 Mar;7(3):571-8
9546821
Am J Hum Genet. 1990 Feb;46(2):229-41
2301393
Hum Mol Genet. 1999 May;8(5):805-12
10196369
Ann Hum Genet. 1963 Nov;27:175-82
14081488
Ment Retard Dev Disabil Res Rev. 2004;10(4):272-83
15666342
Am J Med Genet B Neuropsychiatr Genet. 2003 Aug 15;121B(1):95-9
12898582
Am J Hum Genet. 2001 Aug;69(2):463-6
11452364
Hum Hered. 2004;57(2):100-8
15192282
Acta Psychiatr Scand. 2001 Jun;103(6):428-34
11401656
Am J Hum Genet. 2003 Oct;73(4):886-97
13680528
Genet Epidemiol. 1999;17 Suppl 1:S749-54
10597525
Hum Hered. 2002;53(1):23-35
11901268
Am J Hum Genet. 2001 Aug;69(2):327-40
11452361
Am J Hum Genet. 2002 Apr;70(4):1058-61
11875756
J Autism Dev Disord. 1994 Oct;24(5):659-85
7814313
Am J Hum Genet. 1998 Oct;63(4):947-54
9758634
Indian J Dermatol Venereol Leprol. 2003 Nov-Dec;69(6):423-4
17642958
Am J Hum Genet. 1976 Sep;28(5):528-9
984049
Am J Hum Genet. 2000 Feb;66(2):508-16
10677311
Am J Hum Genet. 2000 Apr;66(4):1310-27
10731466
Am J Hum Genet. 2004 Dec;75(6):1117-23
15467983
Nat Rev Genet. 2001 Dec;2(12):943-55
11733747
Am J Hum Genet. 2001 Jun;68(6):1514-20
11353400
Ann Hum Genet. 1983 Oct;47(4):311-20
6651220
Hum Hered. 2004;57(1):10-20
15133308
Am J Med Genet. 2002 Jan 8;114(1):99-105
11840513
J Am Acad Child Adolesc Psychiatry. 2003 Jul;42(7):856-63
12819446