Linkage of an alcoholism-related severity phenotype to chromosome 16

Tatiana Foroud, K. K. Bucholz, Howard Edenberg, A. Goate, R. J. Neuman, B. Porjesz, D. L. Koller, J. Rice, T. Reich, L. J. Bierut, C. R. Cloninger, John Nurnberger, T. K. Li, P. M. Conneally, J. A. Tischfield, R. Crowe, V. Hesselbrock, M. Schuckit, H. Begleiter

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

There is substantial evidence for a significant genetic component to the risk for alcoholism. In searching for genes that contribute to this risk, the diagnostic criteria for alcohol dependence may not be the optimal phenotype; rather, creation of a more homogeneous phenotype will lead to a more homogeneous genetic etiology. Items from the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) collected from 830 individuals in 105 alcoholic families were used in a latent class analysis to identify a more homogeneous alcoholism-related phenotype. A four class solution was chosen: class 1, unaffected group; class 2, mildly problematic group; class 3, moderately affected group; and class 4, severely affected group. Classes three and four had high symptom endorsement probabilities for items reflecting severe alcohol dependence and were combined to provide enough sibling pairs for genetic linkage analysis. A total of 291 markers distributed throughout the genome, with an average intermarker distance of 14 cM, were genotyped. Linkage analysis was performed to detect loci underlying classes 3 and 4, the moderately and severely affected alcoholics, of whom 88% met COGA and over 99% met ICD10 criteria for alcohol dependence. Evidence for a locus on chromosome 16, near the marker D16S675, was found with a maximum multipoint lod score of 4.0. Analysis of additional markers on chromosome 16 yielded a lod score of 3.2, narrowed the critical region, and placed the gene between D16S475 and D16S675 in a 15-cM interval.

Original languageEnglish
Pages (from-to)479
Number of pages1
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume81
Issue number6
StatePublished - Nov 6 1998

Fingerprint

Chromosomes, Human, Pair 16
Alcoholism
Phenotype
Lod Score
Alcoholics
Genetic Linkage
Genes
Siblings
Genome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

Linkage of an alcoholism-related severity phenotype to chromosome 16. / Foroud, Tatiana; Bucholz, K. K.; Edenberg, Howard; Goate, A.; Neuman, R. J.; Porjesz, B.; Koller, D. L.; Rice, J.; Reich, T.; Bierut, L. J.; Cloninger, C. R.; Nurnberger, John; Li, T. K.; Conneally, P. M.; Tischfield, J. A.; Crowe, R.; Hesselbrock, V.; Schuckit, M.; Begleiter, H.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 81, No. 6, 06.11.1998, p. 479.

Research output: Contribution to journalArticle

Foroud, T, Bucholz, KK, Edenberg, H, Goate, A, Neuman, RJ, Porjesz, B, Koller, DL, Rice, J, Reich, T, Bierut, LJ, Cloninger, CR, Nurnberger, J, Li, TK, Conneally, PM, Tischfield, JA, Crowe, R, Hesselbrock, V, Schuckit, M & Begleiter, H 1998, 'Linkage of an alcoholism-related severity phenotype to chromosome 16', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 81, no. 6, pp. 479.
Foroud, Tatiana ; Bucholz, K. K. ; Edenberg, Howard ; Goate, A. ; Neuman, R. J. ; Porjesz, B. ; Koller, D. L. ; Rice, J. ; Reich, T. ; Bierut, L. J. ; Cloninger, C. R. ; Nurnberger, John ; Li, T. K. ; Conneally, P. M. ; Tischfield, J. A. ; Crowe, R. ; Hesselbrock, V. ; Schuckit, M. ; Begleiter, H. / Linkage of an alcoholism-related severity phenotype to chromosome 16. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 1998 ; Vol. 81, No. 6. pp. 479.
@article{15922d36f196412f8b389e36a2d606ea,
title = "Linkage of an alcoholism-related severity phenotype to chromosome 16",
abstract = "There is substantial evidence for a significant genetic component to the risk for alcoholism. In searching for genes that contribute to this risk, the diagnostic criteria for alcohol dependence may not be the optimal phenotype; rather, creation of a more homogeneous phenotype will lead to a more homogeneous genetic etiology. Items from the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) collected from 830 individuals in 105 alcoholic families were used in a latent class analysis to identify a more homogeneous alcoholism-related phenotype. A four class solution was chosen: class 1, unaffected group; class 2, mildly problematic group; class 3, moderately affected group; and class 4, severely affected group. Classes three and four had high symptom endorsement probabilities for items reflecting severe alcohol dependence and were combined to provide enough sibling pairs for genetic linkage analysis. A total of 291 markers distributed throughout the genome, with an average intermarker distance of 14 cM, were genotyped. Linkage analysis was performed to detect loci underlying classes 3 and 4, the moderately and severely affected alcoholics, of whom 88{\%} met COGA and over 99{\%} met ICD10 criteria for alcohol dependence. Evidence for a locus on chromosome 16, near the marker D16S675, was found with a maximum multipoint lod score of 4.0. Analysis of additional markers on chromosome 16 yielded a lod score of 3.2, narrowed the critical region, and placed the gene between D16S475 and D16S675 in a 15-cM interval.",
author = "Tatiana Foroud and Bucholz, {K. K.} and Howard Edenberg and A. Goate and Neuman, {R. J.} and B. Porjesz and Koller, {D. L.} and J. Rice and T. Reich and Bierut, {L. J.} and Cloninger, {C. R.} and John Nurnberger and Li, {T. K.} and Conneally, {P. M.} and Tischfield, {J. A.} and R. Crowe and V. Hesselbrock and M. Schuckit and H. Begleiter",
year = "1998",
month = "11",
day = "6",
language = "English",
volume = "81",
pages = "479",
journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",
issn = "1552-4841",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Linkage of an alcoholism-related severity phenotype to chromosome 16

AU - Foroud, Tatiana

AU - Bucholz, K. K.

AU - Edenberg, Howard

AU - Goate, A.

AU - Neuman, R. J.

AU - Porjesz, B.

AU - Koller, D. L.

AU - Rice, J.

AU - Reich, T.

AU - Bierut, L. J.

AU - Cloninger, C. R.

AU - Nurnberger, John

AU - Li, T. K.

AU - Conneally, P. M.

AU - Tischfield, J. A.

AU - Crowe, R.

AU - Hesselbrock, V.

AU - Schuckit, M.

AU - Begleiter, H.

PY - 1998/11/6

Y1 - 1998/11/6

N2 - There is substantial evidence for a significant genetic component to the risk for alcoholism. In searching for genes that contribute to this risk, the diagnostic criteria for alcohol dependence may not be the optimal phenotype; rather, creation of a more homogeneous phenotype will lead to a more homogeneous genetic etiology. Items from the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) collected from 830 individuals in 105 alcoholic families were used in a latent class analysis to identify a more homogeneous alcoholism-related phenotype. A four class solution was chosen: class 1, unaffected group; class 2, mildly problematic group; class 3, moderately affected group; and class 4, severely affected group. Classes three and four had high symptom endorsement probabilities for items reflecting severe alcohol dependence and were combined to provide enough sibling pairs for genetic linkage analysis. A total of 291 markers distributed throughout the genome, with an average intermarker distance of 14 cM, were genotyped. Linkage analysis was performed to detect loci underlying classes 3 and 4, the moderately and severely affected alcoholics, of whom 88% met COGA and over 99% met ICD10 criteria for alcohol dependence. Evidence for a locus on chromosome 16, near the marker D16S675, was found with a maximum multipoint lod score of 4.0. Analysis of additional markers on chromosome 16 yielded a lod score of 3.2, narrowed the critical region, and placed the gene between D16S475 and D16S675 in a 15-cM interval.

AB - There is substantial evidence for a significant genetic component to the risk for alcoholism. In searching for genes that contribute to this risk, the diagnostic criteria for alcohol dependence may not be the optimal phenotype; rather, creation of a more homogeneous phenotype will lead to a more homogeneous genetic etiology. Items from the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) collected from 830 individuals in 105 alcoholic families were used in a latent class analysis to identify a more homogeneous alcoholism-related phenotype. A four class solution was chosen: class 1, unaffected group; class 2, mildly problematic group; class 3, moderately affected group; and class 4, severely affected group. Classes three and four had high symptom endorsement probabilities for items reflecting severe alcohol dependence and were combined to provide enough sibling pairs for genetic linkage analysis. A total of 291 markers distributed throughout the genome, with an average intermarker distance of 14 cM, were genotyped. Linkage analysis was performed to detect loci underlying classes 3 and 4, the moderately and severely affected alcoholics, of whom 88% met COGA and over 99% met ICD10 criteria for alcohol dependence. Evidence for a locus on chromosome 16, near the marker D16S675, was found with a maximum multipoint lod score of 4.0. Analysis of additional markers on chromosome 16 yielded a lod score of 3.2, narrowed the critical region, and placed the gene between D16S475 and D16S675 in a 15-cM interval.

UR - http://www.scopus.com/inward/record.url?scp=13044305029&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13044305029&partnerID=8YFLogxK

M3 - Article

VL - 81

SP - 479

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

SN - 1552-4841

IS - 6

ER -