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PMID: 16537441 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Linkage analysis of quantitative traits for obesity, diabetes, hypertension, and dyslipidemia on the island of Kosrae, Federated States of Micronesia.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 10 ·2006-03-07 ·Pages 3502-9

Shmulewitz D, Heath SC, Blundell ML, Han Z, Sharma R, Salit J, Auerbach SB, Signorini S, Breslow JL, Stoffel M, Friedman JM

Abstract

Obesity, diabetes, hypertension, and heart disease are highly heritable conditions that in aggregate are the major causes of morbidity and mortality in the developed world and are growing problems in developing countries. To map the causal genes, we conducted a population screen for these conditions on the Pacific Island of Kosrae. Family history and genetic data were used to construct a pedigree for the island. Analysis of the pedigree showed highly significant heritability for the metabolic traits under study. DNA samples from 2,188 participants were genotyped with 405 microsatellite markers with an average intermarker distance of 11 cM. A protocol using loki, a Markov chain Monte Carlo sampling method, was developed to analyze the Kosraen pedigree for height, a model quantitative trait. Robust quantitative trait loci for height were found on 10q21 and 1p31. This protocol was used to map a set of metabolic traits, including plasma leptin to chromosome region 5q35; systolic blood pressure to 20p12; total cholesterol to 19p13, 12q24, and 16qter; hip circumference to 10q25 and 4q23; body mass index to 18p11 and 20q13; apolipoprotein B to 2p24-25; weight to 18q21; and fasting blood sugar to 1q31-1q43. Several of these same chromosomal regions have been identified in previous studies validating the use of loki. These studies add information about the genetics of the metabolic syndrome and establish an analytical approach for linkage analysis of complex pedigrees. These results also lay the foundation for whole genome scans with dense sets of SNPs aimed to identifying causal genes.

MeSH Terms
Body Height/genetics Chromosome Mapping Diabetes Mellitus/genetics Dyslipidemias/genetics Female Genetic Linkage Genotype Humans Hypertension/genetics Male Markov Chains Metabolic Syndrome/genetics Micronesia Microsatellite Repeats Models, Genetic Monte Carlo Method Obesity/genetics Pedigree Quantitative Trait Loci
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Shmulewitz Dvora
Department of Biostatistics, Columbia University, New York, NY 10032, USA.
Heath Simon C
Blundell Maude L
Han Zhihua
Sharma Ratnendra
Salit Jacqueline
Auerbach Steven B
Signorini Stefano
Breslow Jan L
Stoffel Markus
Friedman Jeffrey M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0510156103
Published
2006-03-07
Epub
2006-00-28
Pages
3502-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1533774
Subset
IM
Grants
NIGMS NIH HHS · T32 GM007982 · United States
NIMH NIH HHS · T32 MH065213 · United States
NIGMS NIH HHS · GM07982 · United States
NIMH NIH HHS · T32MH65213 · United States
External Links
PubMed source DOI: 10.1073/pnas.0510156103 PMC Full Text View journal details
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