Evidence for an inflammatory bowel disease locus on chromosome 3p26: Linkage, transmission/disequilibrium and partitioning of linkage

Richard H. Duerr; M. Michael Barmada; Leilei Zhang; Jean Paul Achkar; Judy H. Cho; Stephen B. Hanauer; Steven R. Brant; Theodore M. Bayless; Robert N. Baldassano; Daniel E. Weeks

doi:10.1093/hmg/11.21.2599

Evidence for an inflammatory bowel disease locus on chromosome 3p26: Linkage, transmission/disequilibrium and partitioning of linkage

Richard H. Duerr^*, M. Michael Barmada, Leilei Zhang, Jean Paul Achkar, Judy H. Cho, Stephen B. Hanauer, Steven R. Brant, Theodore M. Bayless, Robert N. Baldassano, Daniel E. Weeks

^*Corresponding author for this work

Medicine, Gastroenterology Division

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

Abstract

Crohn's disease and ulcerative colitis, the two major forms of idiopathic inflammatory bowel disease (IBD), are heritable, complex traits that appear to share some but not all susceptibility loci. We report that transmission/disequilibrium test analysis of a Crohn's disease genome scan dataset has detected an inflammatory bowel disease locus on chromosome 3p26 (nominal P=0.000052 and genome-wide corrected P=0.039 at D3S1297). An allele sharing method shows significant linkage (multipoint lod=3.69) in a larger, independent sample of inflammatory bowel disease-affected sibling pairs. A survey of 16 chromosome 3p26 short tandem repeat polymorphisms in a combined sample of 234 independent nuclear families with 324 IBD-affected sibling pairs shows significant linkage to chromosome 3p26 (multipoint lod=3.78) and significant transmission/disequilibrium test results at two adjacent markers (nominal P values in two different transmission/disequilibrium analysis methods=0.00011 and 0.0011 for the first marker, and 0.00071 and 0.00013 for the second marker). There is highly significant under-transmission of a common allele and modest over-transmission of other alleles at both markers. Families with no transmission to affected individuals of the under-transmitted alleles show significant linkage (multipoint lod=4.50) that is significantly greater in four simulation studies (P=0.0001, 0.0000625, 0.0000625 and 0.0000625, respectively) than the linkage evidence in families with transmission of the under-transmitted alleles (multipoint lod = 0.12). Thus, the existence of an inflammatory bowel disease locus on chromosome 3p26 is supported by significant linkage, transmission/disequilibrium and partitioning of linkage evidence.

Original language	English (US)
Pages (from-to)	2599-2606
Number of pages	8
Journal	Human molecular genetics
Volume	11
Issue number	21
DOIs	https://doi.org/10.1093/hmg/11.21.2599
State	Published - Oct 1 2002

Funding

Genotyping and statistical analyses were funded by a grant to R.H.D. from the Crohn’s & Colitis Foundation of America. Study subject recruitment was funded by the Scaife Family Foundation (R.H.D.), NIH/NIDDK R01DK55731 (J.H.C.), the Gastrointestinal Research Foundation (J.H.C.), the Meyerhoff IBD Center (S.R.B. and T.M.B.), the Crohn’s & Colitis Foundation of America (S.R.B. and T.M.B.) and NIH/NCRR GCRC RR00052 (S.R.B.).

ASJC Scopus subject areas

Genetics(clinical)
Genetics
Molecular Biology

Access to Document

10.1093/hmg/11.21.2599

Cite this

Duerr, R. H., Barmada, M. M., Zhang, L., Achkar, J. P., Cho, J. H., Hanauer, S. B., Brant, S. R., Bayless, T. M., Baldassano, R. N., & Weeks, D. E. (2002). Evidence for an inflammatory bowel disease locus on chromosome 3p26: Linkage, transmission/disequilibrium and partitioning of linkage. Human molecular genetics, 11(21), 2599-2606. https://doi.org/10.1093/hmg/11.21.2599

@article{3abafa23c1a543eabc6d29fc04977e49,

title = "Evidence for an inflammatory bowel disease locus on chromosome 3p26: Linkage, transmission/disequilibrium and partitioning of linkage",

abstract = "Crohn's disease and ulcerative colitis, the two major forms of idiopathic inflammatory bowel disease (IBD), are heritable, complex traits that appear to share some but not all susceptibility loci. We report that transmission/disequilibrium test analysis of a Crohn's disease genome scan dataset has detected an inflammatory bowel disease locus on chromosome 3p26 (nominal P=0.000052 and genome-wide corrected P=0.039 at D3S1297). An allele sharing method shows significant linkage (multipoint lod=3.69) in a larger, independent sample of inflammatory bowel disease-affected sibling pairs. A survey of 16 chromosome 3p26 short tandem repeat polymorphisms in a combined sample of 234 independent nuclear families with 324 IBD-affected sibling pairs shows significant linkage to chromosome 3p26 (multipoint lod=3.78) and significant transmission/disequilibrium test results at two adjacent markers (nominal P values in two different transmission/disequilibrium analysis methods=0.00011 and 0.0011 for the first marker, and 0.00071 and 0.00013 for the second marker). There is highly significant under-transmission of a common allele and modest over-transmission of other alleles at both markers. Families with no transmission to affected individuals of the under-transmitted alleles show significant linkage (multipoint lod=4.50) that is significantly greater in four simulation studies (P=0.0001, 0.0000625, 0.0000625 and 0.0000625, respectively) than the linkage evidence in families with transmission of the under-transmitted alleles (multipoint lod = 0.12). Thus, the existence of an inflammatory bowel disease locus on chromosome 3p26 is supported by significant linkage, transmission/disequilibrium and partitioning of linkage evidence.",

author = "Duerr, {Richard H.} and Barmada, {M. Michael} and Leilei Zhang and Achkar, {Jean Paul} and Cho, {Judy H.} and Hanauer, {Stephen B.} and Brant, {Steven R.} and Bayless, {Theodore M.} and Baldassano, {Robert N.} and Weeks, {Daniel E.}",

note = "Funding Information: Genotyping and statistical analyses were funded by a grant to R.H.D. from the Crohn{\textquoteright}s & Colitis Foundation of America. Study subject recruitment was funded by the Scaife Family Foundation (R.H.D.), NIH/NIDDK R01DK55731 (J.H.C.), the Gastrointestinal Research Foundation (J.H.C.), the Meyerhoff IBD Center (S.R.B. and T.M.B.), the Crohn{\textquoteright}s & Colitis Foundation of America (S.R.B. and T.M.B.) and NIH/NCRR GCRC RR00052 (S.R.B.).",

year = "2002",

month = oct,

day = "1",

doi = "10.1093/hmg/11.21.2599",

language = "English (US)",

volume = "11",

pages = "2599--2606",

journal = "Human molecular genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "21",

}

TY - JOUR

T1 - Evidence for an inflammatory bowel disease locus on chromosome 3p26

T2 - Linkage, transmission/disequilibrium and partitioning of linkage

AU - Duerr, Richard H.

AU - Barmada, M. Michael

AU - Zhang, Leilei

AU - Achkar, Jean Paul

AU - Cho, Judy H.

AU - Hanauer, Stephen B.

AU - Brant, Steven R.

AU - Bayless, Theodore M.

AU - Baldassano, Robert N.

AU - Weeks, Daniel E.

N1 - Funding Information: Genotyping and statistical analyses were funded by a grant to R.H.D. from the Crohn’s & Colitis Foundation of America. Study subject recruitment was funded by the Scaife Family Foundation (R.H.D.), NIH/NIDDK R01DK55731 (J.H.C.), the Gastrointestinal Research Foundation (J.H.C.), the Meyerhoff IBD Center (S.R.B. and T.M.B.), the Crohn’s & Colitis Foundation of America (S.R.B. and T.M.B.) and NIH/NCRR GCRC RR00052 (S.R.B.).

PY - 2002/10/1

Y1 - 2002/10/1

N2 - Crohn's disease and ulcerative colitis, the two major forms of idiopathic inflammatory bowel disease (IBD), are heritable, complex traits that appear to share some but not all susceptibility loci. We report that transmission/disequilibrium test analysis of a Crohn's disease genome scan dataset has detected an inflammatory bowel disease locus on chromosome 3p26 (nominal P=0.000052 and genome-wide corrected P=0.039 at D3S1297). An allele sharing method shows significant linkage (multipoint lod=3.69) in a larger, independent sample of inflammatory bowel disease-affected sibling pairs. A survey of 16 chromosome 3p26 short tandem repeat polymorphisms in a combined sample of 234 independent nuclear families with 324 IBD-affected sibling pairs shows significant linkage to chromosome 3p26 (multipoint lod=3.78) and significant transmission/disequilibrium test results at two adjacent markers (nominal P values in two different transmission/disequilibrium analysis methods=0.00011 and 0.0011 for the first marker, and 0.00071 and 0.00013 for the second marker). There is highly significant under-transmission of a common allele and modest over-transmission of other alleles at both markers. Families with no transmission to affected individuals of the under-transmitted alleles show significant linkage (multipoint lod=4.50) that is significantly greater in four simulation studies (P=0.0001, 0.0000625, 0.0000625 and 0.0000625, respectively) than the linkage evidence in families with transmission of the under-transmitted alleles (multipoint lod = 0.12). Thus, the existence of an inflammatory bowel disease locus on chromosome 3p26 is supported by significant linkage, transmission/disequilibrium and partitioning of linkage evidence.

AB - Crohn's disease and ulcerative colitis, the two major forms of idiopathic inflammatory bowel disease (IBD), are heritable, complex traits that appear to share some but not all susceptibility loci. We report that transmission/disequilibrium test analysis of a Crohn's disease genome scan dataset has detected an inflammatory bowel disease locus on chromosome 3p26 (nominal P=0.000052 and genome-wide corrected P=0.039 at D3S1297). An allele sharing method shows significant linkage (multipoint lod=3.69) in a larger, independent sample of inflammatory bowel disease-affected sibling pairs. A survey of 16 chromosome 3p26 short tandem repeat polymorphisms in a combined sample of 234 independent nuclear families with 324 IBD-affected sibling pairs shows significant linkage to chromosome 3p26 (multipoint lod=3.78) and significant transmission/disequilibrium test results at two adjacent markers (nominal P values in two different transmission/disequilibrium analysis methods=0.00011 and 0.0011 for the first marker, and 0.00071 and 0.00013 for the second marker). There is highly significant under-transmission of a common allele and modest over-transmission of other alleles at both markers. Families with no transmission to affected individuals of the under-transmitted alleles show significant linkage (multipoint lod=4.50) that is significantly greater in four simulation studies (P=0.0001, 0.0000625, 0.0000625 and 0.0000625, respectively) than the linkage evidence in families with transmission of the under-transmitted alleles (multipoint lod = 0.12). Thus, the existence of an inflammatory bowel disease locus on chromosome 3p26 is supported by significant linkage, transmission/disequilibrium and partitioning of linkage evidence.

UR - http://www.scopus.com/inward/record.url?scp=18644376169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18644376169&partnerID=8YFLogxK

U2 - 10.1093/hmg/11.21.2599

DO - 10.1093/hmg/11.21.2599

M3 - Article

C2 - 12354785

AN - SCOPUS:18644376169

SN - 0964-6906

VL - 11

SP - 2599

EP - 2606

JO - Human molecular genetics

JF - Human molecular genetics

IS - 21

ER -

Evidence for an inflammatory bowel disease locus on chromosome 3p26: Linkage, transmission/disequilibrium and partitioning of linkage

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this