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PMID: 9497255 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians.

American journal of human genetics ·Vol. 62 ·No. 3 ·1998-03-00 ·Pages 659-68

Norman RA, Tataranni PA, Pratley R, Thompson DB, Hanson RL, Prochazka M, Baier L, Ehm MG, Sakul H, Foroud T, Garvey WT, Burns D, Knowler WC, Bennett PH, Bogardus C, Ravussin E

Abstract

An autosomal genomic scan to search for linkage to obesity and energy metabolism was completed in Pima Indians, a population prone to obesity. Obesity was assessed by percent body fat (by hydrodensitometry) and fat distribution (the ratio of waist circumference to thigh circumference). Energy metabolism was measured in a respiratory chamber as 24-h metabolic rate, sleeping metabolic rate, and 24-h respiratory quotient (24RQ), an indicator of the ratio of carbohydrate oxidation to fat oxidation. Five hundred sixteen microsatellite markers with a median spacing of 6.4 cM were analyzed, in 362 siblings who had measurements of body composition and in 220 siblings who had measurements of energy metabolism. These comprised 451 sib pairs in 127 nuclear families, for linkage analysis to obesity, and 236 sib pairs in 82 nuclear families, for linkage analysis to energy metabolism. Pointwise and multipoint methods for regression of sib-pair differences in identity by descent, as well as a sibling-based variance-components method, were used to detect linkage. LOD scores >=2 were found at 11q21-q22, for percent body fat (LOD=2.1; P=.001), at 11q23-q24, for 24-h energy expenditure (LOD=2.0; P=.001), and at 1p31-p21 (LOD=2.0) and 20q11.2 (LOD=3.0; P=.0001), for 24RQ, by pointwise and multipoint analyses. With the variance-components method, the highest LOD score (LOD=2.3 P=.0006) was found at 18q21, for percent body fat, and at 1p31-p21 (LOD=2.8; P=.0003), for 24RQ. Possible candidate genes include LEPR (leptin receptor), at 1p31, and ASIP (agouti-signaling protein), at 20q11.2.

MeSH Terms
Chromosome Mapping Energy Metabolism/genetics Genetic Linkage Humans Indians, North American Lod Score Obesity/genetics
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Norman R A
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ 85016-5319, USA.
Tataranni P A
Pratley R
Thompson D B
Hanson R L
Prochazka M
Baier L
Ehm M G
Sakul H
Foroud T
Garvey W T
Burns D
Knowler W C
Bennett P H
Bogardus C
Ravussin E
References (55)
55 references, click to expand
  1. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects.
    Nat Med. 1995 Nov;1(11):1155-61 PMID: 7584987
  2. Sets of short tandem repeat polymorphisms for efficient linkage screening of the human genome.
    Hum Mol Genet. 1995 Mar;4(3):449-52 PMID: 7795601
  3. Major gene with sex-specific effects influences fat mass in Mexican Americans.
    Genet Epidemiol. 1995;12(5):475-88 PMID: 8557180
  4. Indication for linkage of the human OB gene region with extreme obesity.
    Diabetes. 1996 May;45(5):687-90 PMID: 8621024
  5. Extreme obesity may be linked to markers flanking the human OB gene.
    Diabetes. 1996 May;45(5):691-4 PMID: 8621025
  6. Genetic dissection of complex traits.
    Nat Genet. 1996 Apr;12(4):355-6; author reply 357-8 PMID: 8630483
  7. Genetic dissection of complex traits.
    Nat Genet. 1996 Apr;12(4):356-8 PMID: 8630484
  8. Genetic pleiotropy for resting metabolic rate with fat-free mass and fat mass: the Québec Family Study.
    Obes Res. 1996 Mar;4(2):125-31 PMID: 8681045
  9. The roles of tissue inhibitors of metalloproteinases in tissue remodelling and cell growth.
    Int J Obes Relat Metab Disord. 1996 Mar;20 Suppl 3:S9-15 PMID: 8680484
  10. Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7.
    Am J Hum Genet. 1996 Sep;59(3):694-703 PMID: 8751871
  11. Absence of linkage of obesity and energy metabolism to markers flanking homologues of rodent obesity genes in Pima Indians.
    Diabetes. 1996 Sep;45(9):1229-32 PMID: 8772727
  12. The heritability of body mass index among an international sample of monozygotic twins reared apart.
    Int J Obes Relat Metab Disord. 1996 Jun;20(6):501-6 PMID: 8782724
  13. The antilipolytic effects of insulin and epidermal growth factor in rat adipocytes are mediated by different mechanisms.
    Endocrinology. 1996 Oct;137(10):4181-8 PMID: 8828475
  14. The importance of being independent: sib pair analysis in diabetes.
    Nat Genet. 1996 Oct;14(2):131-2 PMID: 8841179
  15. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1)
    Nature. 1996 Dec 5;384(6608):458-60 PMID: 8945471
  16. Role of the beta 3-adrenergic receptor locus in obesity and noninsulin-dependent diabetes among members of Caucasian families with a diabetic sibling pair.
    J Clin Endocrinol Metab. 1996 Dec;81(12):4422-7 PMID: 8954053
  17. Genomewide search for genes influencing percent body fat in Pima Indians: suggestive linkage at chromosome 11q21-q22. Pima Diabetes Gene Group.
    Am J Hum Genet. 1997 Jan;60(1):166-73 PMID: 8981960
  18. A physical map at 1p31 encompassing the acute insulin response locus and the leptin receptor.
    Genomics. 1997 Jan 15;39(2):227-30 PMID: 9027510
  19. Familiality of physical and metabolic characteristics that predict the development of non-insulin-dependent diabetes mellitus in Pima Indians.
    Am J Hum Genet. 1997 Mar;60(3):651-6 PMID: 9042926
  20. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia.
    Nat Genet. 1997 Mar;15(3):269-72 PMID: 9054939
  21. A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2.
    Nat Genet. 1997 Mar;15(3):273-6 PMID: 9054940
  22. Direct antidiabetic effect of leptin through triglyceride depletion of tissues.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4637-41 PMID: 9114043
  23. Resting metabolic rate in monozygotic and dizygotic twins.
    Acta Genet Med Gemellol (Roma). 1985;34(1-2):41-7 PMID: 4050294
  24. Familial dependence of the resting metabolic rate.
    N Engl J Med. 1986 Jul 10;315(2):96-100 PMID: 3724804
  25. Determinants of 24-hour energy expenditure in man. Methods and results using a respiratory chamber.
    J Clin Invest. 1986 Dec;78(6):1568-78 PMID: 3782471
  26. Three limitations of the body mass index.
    Am J Clin Nutr. 1986 Dec;44(6):996-7 PMID: 3788846
  27. Construction of multilocus genetic linkage maps in humans.
    Proc Natl Acad Sci U S A. 1987 Apr;84(8):2363-7 PMID: 3470801
  28. Reduced rate of energy expenditure as a risk factor for body-weight gain.
    N Engl J Med. 1988 Feb 25;318(8):467-72 PMID: 3340128
  29. Inheritance of the amount and distribution of human body fat.
    Int J Obes. 1988;12(3):205-15 PMID: 3391737
  30. Genetic effect in resting and exercise metabolic rates.
    Metabolism. 1989 Apr;38(4):364-70 PMID: 2657322
  31. A more powerful robust sib-pair test of linkage for quantitative traits.
    Genet Epidemiol. 1989;6(3):435-49 PMID: 2753353
  32. The body-mass index of twins who have been reared apart.
    N Engl J Med. 1990 May 24;322(21):1483-7 PMID: 2336075
  33. Diabetes mellitus in the Pima Indians: incidence, risk factors and pathogenesis.
    Diabetes Metab Rev. 1990 Feb;6(1):1-27 PMID: 2192853
  34. Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ.
    Am J Physiol. 1990 Nov;259(5 Pt 1):E650-7 PMID: 2240203
  35. Obesity in the Pima Indians: its magnitude and relationship with diabetes.
    Am J Clin Nutr. 1991 Jun;53(6 Suppl):1543S-1551S PMID: 2031485
  36. Health implications of obesity.
    Am J Clin Nutr. 1991 Jun;53(6 Suppl):1595S-1603S PMID: 2031492
  37. Spontaneous physical activity and obesity: cross-sectional and longitudinal studies in Pima Indians.
    Am J Physiol. 1992 Aug;263(2 Pt 1):E296-300 PMID: 1514610
  38. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.
    Science. 1993 Jan 1;259(5091):87-91 PMID: 7678183
  39. A genetic map of chromosome 20q12-q13.1: multiple highly polymorphic microsatellite and RFLP markers linked to the maturity-onset diabetes of the young (MODY) locus.
    Am J Hum Genet. 1993 Jan;52(1):110-23 PMID: 8094595
  40. Segregation analysis of fat mass and other body composition measures derived from underwater weighing.
    Am J Hum Genet. 1993 May;52(5):967-73 PMID: 8488846
  41. Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the beta 3-adrenergic-receptor gene.
    N Engl J Med. 1995 Aug 10;333(6):343-7 PMID: 7609750
  42. Linkage between obesity and a marker near the tumor necrosis factor-alpha locus in Pima Indians.
    J Clin Invest. 1995 Jul;96(1):158-62 PMID: 7615786
  43. Adenosine effects upon insulin action on lipolysis and glucose transport in human adipocytes.
    Mol Cell Biochem. 1995 Mar 23;144(2):147-51 PMID: 7623786
  44. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results.
    Nat Genet. 1995 Nov;11(3):241-7 PMID: 7581446
  45. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians.
    N Engl J Med. 1993 Dec 30;329(27):1988-92 PMID: 8247074
  46. Robust variance-components approach for assessing genetic linkage in pedigrees.
    Am J Hum Genet. 1994 Mar;54(3):535-43 PMID: 8116623
  47. Metabolic predictors of obesity: cross-sectional versus longitudinal data.
    Int J Obes Relat Metab Disord. 1993 Dec;17 Suppl 3:S28-31; discussion S41-2 PMID: 8124397
  48. Obesity in Pima Indians: genetic segregation analyses of body mass index complicated by temporal increases in obesity.
    Hum Biol. 1994 Apr;66(2):251-74 PMID: 8194846
  49. Increasing prevalence of overweight among US adults. The National Health and Nutrition Examination Surveys, 1960 to 1991.
    JAMA. 1994 Jul 20;272(3):205-11 PMID: 8022039
  50. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor.
    Nature. 1994 Oct 27;371(6500):799-802 PMID: 7935841
  51. Molecular structure and chromosomal mapping of the human homolog of the agouti gene.
    Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9760-4 PMID: 7937887
  52. Comparison of fluorescence-based semi-automated genotyping of multiple microsatellite loci with autoradiographic techniques.
    Genomics. 1994 Jul 1;22(1):46-54 PMID: 7959791
  53. Empirical threshold values for quantitative trait mapping.
    Genetics. 1994 Nov;138(3):963-71 PMID: 7851788
  54. Structure and function of ASP, the human homolog of the mouse agouti gene.
    Hum Mol Genet. 1995 Feb;4(2):223-30 PMID: 7757071
  55. The effects of wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, on insulin-stimulated glucose transport, GLUT4 translocation, antilipolysis, and DNA synthesis.
    Cell Signal. 1995 May;7(4):365-76 PMID: 8527305
Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/301758
Published
1998-03-00
Pages
659-68
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1376952
Subset
IM
Grants
NCRR NIH HHS · 1 P41 RR03655 · United States
NIDDK NIH HHS · DK-47461 · United States
External Links
PubMed source DOI: 10.1086/301758 PMC Full Text View journal details
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