Contribution of Known and Unknown Susceptibility Genes to Early-Onset Diabetes in Scandinavia

Lindgren, Cecilia M.; Widén, Elisabeth; Tuomi, Tiinamaija; Li, Haiyan; Almgren, Peter; Kanninen, Timo; Melander, Olle; Weng, Jianping; Lehto, Markku; Groop, Leif

doi:10.2337/diabetes.51.5.1609

Cited by 29 publications

(14 citation statements)

References 58 publications

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“…No other genome-wide scans of MODY families have been published (with the exception of the five Swedish families in this study that were part of a young-onset type 2 diabetes genome-wide scan) (26), and so we cannot look for regions of linkage overlapping with ours using the same phenotype. Additional early-onset families with type 2 diabetes have been identified (42,43), and our regions will provide starting places for any future genome-wide screens of MODYX or early-onset type 2 diabetic families.…”

Section: Discussionmentioning

confidence: 99%

“…These include regions on chromosome 4 and 20 (45) in Ashkenazi Jews, chromosome 6 in Finnish subjects ranging in age at diagnosis from 29 to 44 years (46), chromosome 5 in Swedish subjects (47), chromosome 3 in French subjects diagnosed with type 2 diabetes before 45 years of age (48), chromosomes 5 and 22 in U.K. subjects from families where the average age at diagnosis was Ͻ45 years (49), and chromosomes 1, 5, 7, 8, 11, 15, and 21 in Swedish/Finnish subjects (26). Although it is not clear from all these studies the exact ages at diagnosis, most appear to represent subjects diagnosed under the age of 45 years.…”

Section: Discussionmentioning

confidence: 99%

“…Before linkage analysis, Mendel conflicts due to misinterpretation of traces were resolved through rescoring in Genetic Profiler. The Swedish Finnish Genome-Wide Scan has been described in detail elsewhere (26). Strategy of data pooling.…”

Section: Fig 2-continuedmentioning

confidence: 99%

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A Genome-Wide Scan in Families With Maturity-Onset Diabetes of the Young

et al. 2003

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A Genome-Wide Scan in Families With Maturity-Onset Diabetes of the Young

et al. 2003

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“…At least two research groups (14,15) have reported linkages for diabetic nephropathy on 18q. Lindgren et al (16) found suggestive linkage on 18q12 for early-onset diabetes. A locus for type 1 diabetes (IDDM6, MIM 601941) also mapped to 18q21 (17).…”

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confidence: 99%

A Quantitative Trait Locus Influencing Fasting Plasma Glucose in Chromosome Region 18q22-23

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Ding

et al. 2004

Diabetes

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Fasting plasma glucose is a multigenic trait related to both diabetes and obesity. We performed a genome scan for quantitative fasting plasma glucose levels in 320 families (1,514 subjects), segregating extreme obesity and normal weight using 382 autosomal microsatellite markers. We found significant linkages on 18q22-23 using family regression (logarithm of odds [LOD] 3.67, P ‫؍‬ 0.00002, D18S1371 at 116 cM) and variance components (LOD 4.48, P < 0.00001) methods. Evidence for linkage remained strong when restricted to European Americans (260 families, 1,258 individuals). After an additional 60 families were added, the linkage signal strengthened (LOD 6.59). The result on 18q22-23 remained significant, even after controlling for both BMI and diabetes status. We also found suggestive linkages on chromosomes 2 (LOD 1.58, 216 cM) and 7 (LOD 1.78, 163 cM). Our results suggest that there is a quantitative trait locus in chromosome region 18q22-23 that influences fasting glucose levels and may play a role in the pathogenesis of type 2 diabetes. The strength of the serum glucose results after controlling for BMI suggests that this putative gene does not influence glucose levels merely through an effect on obesity.

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“…Shaw et al (47) observed a susceptibility locus for late-onset type 2 diabetes linked to marker D12S321 (65 cM) on chromosome 12, with an LOD score 3.65. In early-onset diabetic Scandinavians (48), an NPL score of 1.9 was documented on chromosome 18 near marker D18S535 (64 cM). This marker is 16 cM upstream of our signal for 2-h insulin concentrations.…”

Section: Resultsmentioning

confidence: 99%

Genome-Wide Scans Reveal Quantitative Trait Loci on 8p and 13q Related to Insulin Action and Glucose Metabolism

et al. 2004

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T ype 2 diabetes/insulin resistance is a major component of the metabolic syndrome, which also includes hyperlipidemia, central obesity, hypertension, and cardiovascular diseases. Dramatic changes in environment and lifestyle have led to an epidemic increase in the number of diabetes patients, with the current 160 million expected to reach 220 million in 2010 and 300 million in 2025 (1,2). Its familial nature and differential prevalence in diverse populations suggest that type 2 diabetes is the consequence of the interactions of genetic and environmental factors (3). According to Permutt and Hattersley (4) and Rich (5), the best-fit genetic model, inferred from most of the previous genetic studies for type 2 diabetes, involves a few genes with moderate effect, superimposed on a polygenic background.Linkage studies have implicated many regions on a number of chromosomes as being related to type 2 diabetes phenotypes. Among them, regions on chromosomes 1q, 2q, 3q, 9q, 10q, and 11q have been replicated (6). In addition, there is evidence of a quantitative trait locus (QTL) on chromosome 3, which may be influencing the expression of the metabolic syndrome (7,8). However, more genetic investigations in different populations are necessary to further our understanding of this complex condition.In the present study, genome-wide scans for insulin resistance-a major risk factor for type 2 diabetes-were conducted in Mexican Americans from the San Antonio Family Heart Study (SAFHS) (9). The insulin resistance traits examined by multipoint analysis included fasting and 2-h glucose, fasting and 2-h insulin, and the calculated insulin resistance indexes (homeostasis model assessment of insulin resistance index [HOMA-IR], quantitative insulin sensitivity check index [QUICKI], corrected insulin response [CIR], and insulin response to glucose [IRG]). RESEARCH DESIGN AND METHODSSubjects and data. Mexican Americans who are from San Antonio, Texas, and have been participating in the SAFHS (9) are the subjects of this study. Probands were selected randomly from a census tract in San Antonio of Ͼ90% Mexican-American residency, without regard to any preexisting medical conditions. Probands who were selected were 40 -60 years of age, had a spouse who was willing to participate, and had at least six offspring who were CIR, corrected insulin response; HOMA-IR, homeostasis model assessment of insulin resistance index; IBD, identity-by-descent; IPF-1, insulin promotor factor-1; IRG, insulin response to glucose; LOD, logarithm of odds; MODY, maturity-onset diabetes of the young; NPL, nonparametric linkage; QTL, quantitative trait locus; QUICKI, quantitative insulin sensitivity check index.

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Contribution of Known and Unknown Susceptibility Genes to Early-Onset Diabetes in Scandinavia

Cited by 29 publications

References 58 publications

A Genome-Wide Scan in Families With Maturity-Onset Diabetes of the Young

A Genome-Wide Scan in Families With Maturity-Onset Diabetes of the Young

A Quantitative Trait Locus Influencing Fasting Plasma Glucose in Chromosome Region 18q22-23

Genome-Wide Scans Reveal Quantitative Trait Loci on 8p and 13q Related to Insulin Action and Glucose Metabolism

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