A Gene Conferring Susceptibility to Type 2 Diabetes in Conjunction With Obesity Is Located on Chromosome 18p11

Parker, Alex; Meyer, Joanne M.; Lewitzky, Steve; Rennich, Jean S.; Chan, Gayun; Thomas, Jeffrey; Orho‐Melander, Marju; Lehtovirta, Mikko; Forsblom, Carol; Hyrkkö, A; Carlsson, Martin; Lindgren, Cecilia M.; Groop, Leif

doi:10.2337/diabetes.50.3.675

Cited by 84 publications

(63 citation statements)

References 37 publications

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“…Although our results in some respect overlap with others in regard to 3q, 15q, and 20q, we observed no linkage in 2q37 (29,43), 10q (44), 11q23-q25 (36), 12q24 (45), or 18p11 (46). Considering our limited sample size (224 sib-pairs), this failure of replication may be explained by different ethnic backgrounds or our limited power to detect linkage with genes having marginal effects in the Japanese population.…”

Section: Discussioncontrasting

confidence: 52%

Genome-Wide Search for Type 2 Diabetes in Japanese Affected Sib-Pairs Confirms Susceptibility Genes on 3q, 15q, and 20q and Identifies Two New Candidate Loci on 7p and 11p

et al. 2002

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The genetic background that predisposes the Japanese population to type 2 diabetes is largely unknown. Therefore, we conducted a 10-cM genome-wide scan for type 2 diabetes traits in the 359 affected individuals from 159 families, yielding 224 affected sib-pairs of Japanese origin. Nonparametric multipoint linkage analyses performed in the whole population showed one suggestive linked region on 11p13-p12 (maximum logarithm of odds score [MLS] 3.08, near Pax6) and seven potentially linked regions (MLS >1.17) at 1p36-p32, 2q34, 3q26-q28, 6p23, 7p22-p21, 15q13-q21, and 20q12-q13 (near the gene for hepatocyte nuclear factor-4␣ [HNF-4␣]). Subset analyses according to maximal BMI and early age at diagnosis added suggestive evidence of linkage with type 2 diabetes at 7p22-p21 (MLS 3.51), 15q13-q21 (MLS 3.91), and 20q12-q13 (MLS 2.32). These results support previous indication for linkage found on chromosome 3q, 15q, and 20q in other populations and identifies two new potential loci on 7p and 11p that may confer genetic risk for type 2 diabetes in the Japanese population.

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Section: Discussioncontrasting

confidence: 52%

Genome-Wide Search for Type 2 Diabetes in Japanese Affected Sib-Pairs Confirms Susceptibility Genes on 3q, 15q, and 20q and Identifies Two New Candidate Loci on 7p and 11p

et al. 2002

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“…Also within this region, near the marker D17S1301, a linkage peak with the LOD score of 1.29 has been found in type 2 diabetes in Finland and southern Sweden (42). In an ethnic group with similar ancestors to our own, Caucasians from Quebec, a linkage was found with a quantitative trait locus influencing abdominal subcutaneous fat that overlaps this region (43).…”

Section: Discussionmentioning

confidence: 86%

Genome-wide Linkage Analysis for Severe Obesity in French Caucasians Finds Significant Susceptibility Locus on Chromosome 19q

et al. 2004

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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 >35 kg/m 2 ), and 84.8% of the nuclear families possessed >1 morbidly obese sibling (BMI >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 >35 phenotypic subset, and 5q and 10q for an inclusive BMI >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 >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 >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 >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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“…However, we replicated a previous linkage signal for BMI on 18p11 in the subjects living in the Pacific Island of Kosrae. 47 The same locus was also reported to be linked to type 2 diabetes mellitus 48,49 and percent FM in men. 50 Kraja et al 51 conducted genome-wide linkage analysis on metabolic risk factors.…”

Section: Discussionmentioning

confidence: 85%

Genome-wide scan revealed genetic loci for energy metabolism in Hispanic children and adolescents

et al. 2008

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Objective: Genome-wide scans were conducted in search for genetic locations linked to energy expenditure and substrate oxidation in children. Design: Pedigreed data of 1030 Hispanic children and adolescents were from the Viva La Familia Study which was designed to investigate genetic and environmental risk factors for the development of obesity in Hispanic families. A respiratory calorimeter was used to measure 24-h total energy expenditure (TEE), basal metabolic rate (BMR), sleep metabolic rate (SMR), 24-h respiratory quotient (24RQ), basal metabolic respiratory quotient (BMRQ) and sleep respiratory quotient (SRQ). Protein, fat and carbohydrate oxidation (PROOX, FATOX and CHOOX, respectively) were also estimated. All participants were genotyped for 384 single tandem repeat markers spaced an average of 10 cM apart. Computer program SOLAR was used to perform the genetic linkage analyses. Results: Significant linkage for TEE was detected on chromosome 1 near marker D1S2841, with a logarithm of the odds (LOD) score of 4.0. SMR, BMRQ and PROOX were associated with loci on chromosome 18, 17 and 9, respectively, with LOD scores of 4.88, 3.17 and 4.55, respectively. A genome-wide scan of SMR per kg fat-free mass (SpFFM) peaked in the same region as SMR on chromosome 18 (LOD, 5.24). Suggestive linkage was observed for CHOOX and FATOX. Several candidate genes were found in the above chromosomal regions including leptin receptor (LEPR). Conclusion: Regions on chromosomes 1, 9, 17 and 18 harbor genes affecting variation in energy expenditure and substrate oxidation in Hispanic children and adolescents.

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A Gene Conferring Susceptibility to Type 2 Diabetes in Conjunction With Obesity Is Located on Chromosome 18p11

Cited by 84 publications

References 37 publications

Genome-Wide Search for Type 2 Diabetes in Japanese Affected Sib-Pairs Confirms Susceptibility Genes on 3q, 15q, and 20q and Identifies Two New Candidate Loci on 7p and 11p

Genome-Wide Search for Type 2 Diabetes in Japanese Affected Sib-Pairs Confirms Susceptibility Genes on 3q, 15q, and 20q and Identifies Two New Candidate Loci on 7p and 11p

Genome-wide Linkage Analysis for Severe Obesity in French Caucasians Finds Significant Susceptibility Locus on Chromosome 19q

Genome-wide scan revealed genetic loci for energy metabolism in Hispanic children and adolescents

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