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Genome-wide linkage analysis for severe obesity in french caucasians finds significant susceptibility locus on chromosome 19q

Genome-wide linkage analysis for severe obesity in french caucasians finds significant susceptibility locus on chromosome 19q
Genome-wide linkage analysis for severe obesity in french caucasians finds significant susceptibility locus on chromosome 19q
To ascertain whether distinct chromosomal loci existed that were linked to severe obesity, as well as to utilize the increased heritability of this excessive phenotype, we performed a genome-wide scan in severely obese French Caucasians. The 109 selected pedigrees, totaling 447 individuals, required both the proband and a sibling to be severely obese (BMI >or=35 kg/m(2)), and 84.8% of the nuclear families possessed >or=1 morbidly obese sibling (BMI >or=40). Severe and morbid obesity are still relatively rare in France, with rates of 2.5 and 0.6%, respectively. The initial genome scan consisted of 395 evenly spaced microsatellite markers. Six regions were found to have suggestive linkage on 4q, 6cen-q, 17q, and 19q for a BMI >or=35 phenotypic subset, and 5q and 10q for an inclusive BMI >or=27 group. The highest peak on chromosome 19q (logarithm of odds [LOD] = 3.59) was significant by genome scan simulation testing (P = 0.042). These regions then underwent second-stage mapping with an additional set of 42 markers. BMI >or=35 analysis defined regions on 17q23.3-25.1 and 19q13.33-13.43 with an maximum likelihood score LOD of 3.16 and 3.21, respectively. Subsequent pooled data analysis with an additional previous population of 66 BMI >or=35 sib-pairs led to a significant LOD score of 3.8 at the 19q locus (empirical P = 0.023). For more moderate obesity and overweight susceptibility loci, BMI >or=27 analysis confirmed suggestive linkage to chromosome regions 5q14.3-q21.3 (LOD = 2.68) and 10q24.32-26.2 (LOD = 2.47). Plausible positional candidate genes include NR1H2 and TULP2.
0012-1797
1857-1865
Bell, Christopher G.
44982df7-0746-4cdb-bed1-0bdfe68f1a64
Benzinou, Michael
c249c41a-42a0-4741-9c20-5fe15ea780a8
Siddiq, Afshan
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Lecoeur, Cécile
de08c41b-c24a-4ec3-82ef-c58a68a8ed34
Dina, Christian
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Lemainque, Arnaud
f9eb4782-a339-4184-9489-64b976a27516
Clément, Karine
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Basdevant, Arnaud
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Guy-Grand, Bernard
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Mein, Charles A.
c1cc43af-6c34-47a4-a959-5105593bcbde
Meyre, David
023f567d-798c-41f0-a096-2028569a3976
Froguel, Philippe
563ee961-98a3-4aed-98a5-d70e8350ef8c
Bell, Christopher G.
44982df7-0746-4cdb-bed1-0bdfe68f1a64
Benzinou, Michael
c249c41a-42a0-4741-9c20-5fe15ea780a8
Siddiq, Afshan
d21875ef-1bff-48db-b0c3-aac8badd9cf6
Lecoeur, Cécile
de08c41b-c24a-4ec3-82ef-c58a68a8ed34
Dina, Christian
3df025f2-1369-4ea6-84a3-f58994951f68
Lemainque, Arnaud
f9eb4782-a339-4184-9489-64b976a27516
Clément, Karine
bf9b0e87-319a-45e7-ad76-6c9aabd65d04
Basdevant, Arnaud
108df5cd-8d83-4e02-b23d-538e334ca696
Guy-Grand, Bernard
05514d16-bc13-46e3-a5b7-a0f2e3019d03
Mein, Charles A.
c1cc43af-6c34-47a4-a959-5105593bcbde
Meyre, David
023f567d-798c-41f0-a096-2028569a3976
Froguel, Philippe
563ee961-98a3-4aed-98a5-d70e8350ef8c

Bell, Christopher G., Benzinou, Michael, Siddiq, Afshan, Lecoeur, Cécile, Dina, Christian, Lemainque, Arnaud, Clément, Karine, Basdevant, Arnaud, Guy-Grand, Bernard, Mein, Charles A., Meyre, David and Froguel, Philippe (2004) Genome-wide linkage analysis for severe obesity in french caucasians finds significant susceptibility locus on chromosome 19q. Diabetes, 53 (7), 1857-1865. (doi:10.2337/diabetes.53.7.1857). (PMID:15220211)

Record type: Article

Abstract

To ascertain whether distinct chromosomal loci existed that were linked to severe obesity, as well as to utilize the increased heritability of this excessive phenotype, we performed a genome-wide scan in severely obese French Caucasians. The 109 selected pedigrees, totaling 447 individuals, required both the proband and a sibling to be severely obese (BMI >or=35 kg/m(2)), and 84.8% of the nuclear families possessed >or=1 morbidly obese sibling (BMI >or=40). Severe and morbid obesity are still relatively rare in France, with rates of 2.5 and 0.6%, respectively. The initial genome scan consisted of 395 evenly spaced microsatellite markers. Six regions were found to have suggestive linkage on 4q, 6cen-q, 17q, and 19q for a BMI >or=35 phenotypic subset, and 5q and 10q for an inclusive BMI >or=27 group. The highest peak on chromosome 19q (logarithm of odds [LOD] = 3.59) was significant by genome scan simulation testing (P = 0.042). These regions then underwent second-stage mapping with an additional set of 42 markers. BMI >or=35 analysis defined regions on 17q23.3-25.1 and 19q13.33-13.43 with an maximum likelihood score LOD of 3.16 and 3.21, respectively. Subsequent pooled data analysis with an additional previous population of 66 BMI >or=35 sib-pairs led to a significant LOD score of 3.8 at the 19q locus (empirical P = 0.023). For more moderate obesity and overweight susceptibility loci, BMI >or=27 analysis confirmed suggestive linkage to chromosome regions 5q14.3-q21.3 (LOD = 2.68) and 10q24.32-26.2 (LOD = 2.47). Plausible positional candidate genes include NR1H2 and TULP2.

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Accepted/In Press date: 13 April 2004
Published date: July 2004
Organisations: Human Development & Health, Centre for Biological Sciences, MRC Life-Course Epidemiology Unit

Identifiers

Local EPrints ID: 401011
URI: https://eprints.soton.ac.uk/id/eprint/401011
ISSN: 0012-1797
PURE UUID: bdbbee53-e82f-4245-a212-49ee2916378c
ORCID for Christopher G. Bell: ORCID iD orcid.org/0000-0003-4601-1242

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Date deposited: 03 Oct 2016 14:19
Last modified: 20 Jul 2019 00:34

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