Allele frequency heterogeneity in the collaborative study on the genetics of alcoholism (COGA)

N. L. Saccone, J. P. Rice, A. Goate, P. M. Conneally, Howard Edenberg, Tatiana Foroud, John Nurnberger, T. Reich

Research output: Contribution to journalArticle

Abstract

It is well known that admixture of populations having different marker allele frequencies can increase type I error in genome scans with ungenotyped parents, and can cause spurious association in case/control association studies of candidate genes. The Collaborative Study on the Genetics of Alcoholism has ascertained multiplex case families through alcoholic probands. Using markers from a genome screen, we compared allele frequencies among racial groups and found significant and extensive heterogeneity in the COGA data. Differences were also observed at candidate loci commonly studied for association with psychiatric disorders. A total of 609 genotyped founders from COGA case families have identified a racial group to which they belong. While these are broad groupings and diversity of background may be expected within as well as between groups, comparisons were made between the two most represented groups: Caucasian (N=506) and African-American (N=60), using Fisher's exact test. Comparisons of DRD2 and ADH3 were both significant at the 0.001 level; analyses of additional loci are ongoing. These findings confirm the need for caution when using linkage or association methods that depend on assumptions of homogeneity of allele frequencies. Evaluating allele frequency variations throughout the genome in these data will permit more informed genetic analyses.

Original languageEnglish (US)
Pages (from-to)563
Number of pages1
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume96
Issue number4
StatePublished - Aug 7 2000
Externally publishedYes

Fingerprint

Gene Frequency
Alcoholism
Genome
Alcoholics
African Americans
Psychiatry
Case-Control Studies
Parents
Population
Genes

ASJC Scopus subject areas

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

Cite this

Allele frequency heterogeneity in the collaborative study on the genetics of alcoholism (COGA). / Saccone, N. L.; Rice, J. P.; Goate, A.; Conneally, P. M.; Edenberg, Howard; Foroud, Tatiana; Nurnberger, John; Reich, T.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 96, No. 4, 07.08.2000, p. 563.

Research output: Contribution to journalArticle

@article{40649e04a35243e18eb24888b30ac8f2,
title = "Allele frequency heterogeneity in the collaborative study on the genetics of alcoholism (COGA)",
abstract = "It is well known that admixture of populations having different marker allele frequencies can increase type I error in genome scans with ungenotyped parents, and can cause spurious association in case/control association studies of candidate genes. The Collaborative Study on the Genetics of Alcoholism has ascertained multiplex case families through alcoholic probands. Using markers from a genome screen, we compared allele frequencies among racial groups and found significant and extensive heterogeneity in the COGA data. Differences were also observed at candidate loci commonly studied for association with psychiatric disorders. A total of 609 genotyped founders from COGA case families have identified a racial group to which they belong. While these are broad groupings and diversity of background may be expected within as well as between groups, comparisons were made between the two most represented groups: Caucasian (N=506) and African-American (N=60), using Fisher's exact test. Comparisons of DRD2 and ADH3 were both significant at the 0.001 level; analyses of additional loci are ongoing. These findings confirm the need for caution when using linkage or association methods that depend on assumptions of homogeneity of allele frequencies. Evaluating allele frequency variations throughout the genome in these data will permit more informed genetic analyses.",
author = "Saccone, {N. L.} and Rice, {J. P.} and A. Goate and Conneally, {P. M.} and Howard Edenberg and Tatiana Foroud and John Nurnberger and T. Reich",
year = "2000",
month = "8",
day = "7",
language = "English (US)",
volume = "96",
pages = "563",
journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",
issn = "1552-4841",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Allele frequency heterogeneity in the collaborative study on the genetics of alcoholism (COGA)

AU - Saccone, N. L.

AU - Rice, J. P.

AU - Goate, A.

AU - Conneally, P. M.

AU - Edenberg, Howard

AU - Foroud, Tatiana

AU - Nurnberger, John

AU - Reich, T.

PY - 2000/8/7

Y1 - 2000/8/7

N2 - It is well known that admixture of populations having different marker allele frequencies can increase type I error in genome scans with ungenotyped parents, and can cause spurious association in case/control association studies of candidate genes. The Collaborative Study on the Genetics of Alcoholism has ascertained multiplex case families through alcoholic probands. Using markers from a genome screen, we compared allele frequencies among racial groups and found significant and extensive heterogeneity in the COGA data. Differences were also observed at candidate loci commonly studied for association with psychiatric disorders. A total of 609 genotyped founders from COGA case families have identified a racial group to which they belong. While these are broad groupings and diversity of background may be expected within as well as between groups, comparisons were made between the two most represented groups: Caucasian (N=506) and African-American (N=60), using Fisher's exact test. Comparisons of DRD2 and ADH3 were both significant at the 0.001 level; analyses of additional loci are ongoing. These findings confirm the need for caution when using linkage or association methods that depend on assumptions of homogeneity of allele frequencies. Evaluating allele frequency variations throughout the genome in these data will permit more informed genetic analyses.

AB - It is well known that admixture of populations having different marker allele frequencies can increase type I error in genome scans with ungenotyped parents, and can cause spurious association in case/control association studies of candidate genes. The Collaborative Study on the Genetics of Alcoholism has ascertained multiplex case families through alcoholic probands. Using markers from a genome screen, we compared allele frequencies among racial groups and found significant and extensive heterogeneity in the COGA data. Differences were also observed at candidate loci commonly studied for association with psychiatric disorders. A total of 609 genotyped founders from COGA case families have identified a racial group to which they belong. While these are broad groupings and diversity of background may be expected within as well as between groups, comparisons were made between the two most represented groups: Caucasian (N=506) and African-American (N=60), using Fisher's exact test. Comparisons of DRD2 and ADH3 were both significant at the 0.001 level; analyses of additional loci are ongoing. These findings confirm the need for caution when using linkage or association methods that depend on assumptions of homogeneity of allele frequencies. Evaluating allele frequency variations throughout the genome in these data will permit more informed genetic analyses.

UR - http://www.scopus.com/inward/record.url?scp=33749092073&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749092073&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33749092073

VL - 96

SP - 563

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

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

SN - 1552-4841

IS - 4

ER -