TY - JOUR
T1 - A genomewide search finds major susceptibility loci for Gallbladder disease on chromosome 1 in Mexican Americans
AU - Puppala, Sobha
AU - Dodd, Gerald D.
AU - Fowler, Sharon
AU - Arya, Rector
AU - Schneider, Jennifer
AU - Farook, Vidya S.
AU - Granato, Richard
AU - Dyer, Thomas D.
AU - Almasy, Laura
AU - Jenkinson, Christopher P.
AU - Diehl, Andrew K.
AU - Stern, Michael P.
AU - Blangero, John
AU - Duggirala, Ravindranath
N1 - Funding Information:
This study was supported by National Institutes of Health grants DK53889, DK42273, DK47482, and MH59490. We thank the CIDR for performing the new SAFDGS genome scan. We thank Norberto Isaac and Shelley Porter for performing ultrasonograms. We appreciate the nursing and dietetic care provided by the staff of the Frederic C. Bartter General Clinical Research Center at the South Texas Veterans Health Care Systems, Audie Murphy Division. We acknowledge Barbara Chapman, Sherry L. Cummins, Irma Jean Gomez, Rosa M. Pelayo, Margeret de la Garza, Rajeswari Cheruvu, Roy G. Resendez, Allison Mittler, Robin J. Lumpkin, Marcel Fourcaudot, and Paul Streng, for excellent technical support. We thank Drs. Hanna E. Abboud and Ralph A. DeFronzo, for support and encouragement, and Drs. Robin J. Leach and Dawn K. Richardson, for providing help regarding DNA sample/molecular genetic–related issues. We warmly thank the families from SAFDGS for their enthusiasm and cooperation.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2006/3
Y1 - 2006/3
N2 - Gallbladder disease (GBD) is one of the major digestive diseases. Its risk factors include age, sex, obesity, type 2 diabetes, and metabolic syndrome (MS). The prevalence of GBD is high in minority populations, such as Native and Mexican Americans. Ethnic differences, familial aggregation of GBD, and the identification of susceptibility loci for gallstone disease by use of animal models suggest genetic influences on GBD. However, the major susceptibility loci for GBD in human populations have not been identified. Using ultrasound-based information on GBD occurrence and a 10-cM gene map, we performed multipoint variance-components analysis to localize susceptibility loci for GBD. Phenotypic and genotypic data from 715 individuals in 39 low-income Mexican American families participating in the San Antonio Family Diabetes/Gallbladder Study were used. Two GBD phenotypes were defined for the analyses: (1) clinical or symptomatic GBD, the cases of cholecystectomies due to stones confirmed by ultrasound, and (2) total GBD, the clinical GBD cases plus the stone carriers newly diagnosed by ultrasound. With use of the National Cholesterol Education Program/Adult Treatment Panel III criteria, five MS risk factors were defined: increased waist circumference, hypertriglyceredemia, low high-density lipoprotein cholesterol, hypertension, and high fasting glucose. The MS risk-factor score (range 0-5) for a given individual was used as a single, composite covariate in the genetic analyses. After accounting for the effects of age, sex, and MS risk-factor score, we found stronger linkage signals for the symptomatic GBD phenotype. The highest LOD scores (3.7 and 3.5) occurred on chromosome Ip between markers D1S1597 and D1S407 (1p36.21) and near marker D1S255 (1p34.3), respectively. Other genetic locations (chromosomes 2p, 3q, 4p, 8p, 9p, 10p, and 16q) across the genome exhibited some evidence of linkage (LOD ≥ 1.2) to symptomatic GBD. Some of these chromosomal regions corresponded with the genetic locations of Lith loci, which influence gallstone formation in mouse models. In conclusion, we found significant evidence of major genetic determinants of symptomatic GBD on chromosome 1p in Mexican Americans.
AB - Gallbladder disease (GBD) is one of the major digestive diseases. Its risk factors include age, sex, obesity, type 2 diabetes, and metabolic syndrome (MS). The prevalence of GBD is high in minority populations, such as Native and Mexican Americans. Ethnic differences, familial aggregation of GBD, and the identification of susceptibility loci for gallstone disease by use of animal models suggest genetic influences on GBD. However, the major susceptibility loci for GBD in human populations have not been identified. Using ultrasound-based information on GBD occurrence and a 10-cM gene map, we performed multipoint variance-components analysis to localize susceptibility loci for GBD. Phenotypic and genotypic data from 715 individuals in 39 low-income Mexican American families participating in the San Antonio Family Diabetes/Gallbladder Study were used. Two GBD phenotypes were defined for the analyses: (1) clinical or symptomatic GBD, the cases of cholecystectomies due to stones confirmed by ultrasound, and (2) total GBD, the clinical GBD cases plus the stone carriers newly diagnosed by ultrasound. With use of the National Cholesterol Education Program/Adult Treatment Panel III criteria, five MS risk factors were defined: increased waist circumference, hypertriglyceredemia, low high-density lipoprotein cholesterol, hypertension, and high fasting glucose. The MS risk-factor score (range 0-5) for a given individual was used as a single, composite covariate in the genetic analyses. After accounting for the effects of age, sex, and MS risk-factor score, we found stronger linkage signals for the symptomatic GBD phenotype. The highest LOD scores (3.7 and 3.5) occurred on chromosome Ip between markers D1S1597 and D1S407 (1p36.21) and near marker D1S255 (1p34.3), respectively. Other genetic locations (chromosomes 2p, 3q, 4p, 8p, 9p, 10p, and 16q) across the genome exhibited some evidence of linkage (LOD ≥ 1.2) to symptomatic GBD. Some of these chromosomal regions corresponded with the genetic locations of Lith loci, which influence gallstone formation in mouse models. In conclusion, we found significant evidence of major genetic determinants of symptomatic GBD on chromosome 1p in Mexican Americans.
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U2 - 10.1086/500274
DO - 10.1086/500274
M3 - Article
C2 - 16400619
AN - SCOPUS:33344471915
VL - 78
SP - 377
EP - 392
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 3
ER -