A Genome-Wide Search for Type 2 Diabetes Susceptibility Genes in West Africans

Rotimi, Charles N.; Chen, Guanjie; Adeyemo, Adebowale; Furbert-Harris, Paulette; Guass, Debra; Zhou, Jie; Berg, Kate; Adegoke, Olufemi; Amoah, Albert; Owusu, Samuel; Acheampong, Joseph; Agyenim-Boateng, Kofi; Eghan, Benjamin; Oli, Johnnie; Okafor, Godfrey; Ofoegbu, Ester; Osotimehin, Babatunde; Abbiyesuku, F M; Johnson, Thomas; Rufus, Theresa; Fasanmade, O.A; Kittles, Rick A.; Daniel, H.; Chen, Yuanxiu; Dunston, Georgia M.; Collins, Francis S.

doi:10.2337/diabetes.53.3.838

Cited by 93 publications

(79 citation statements)

References 21 publications

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“…Our strongest signals do not overlap with those found by Sale et al, however. A microsatellite scan in West African families (9) reported signals on chromosome 20 (LOD 1.8; 60 -78 cM), which overlapped with a minor peak of similar size in our study at rs1406966 (LOD 1.77; 62 cM). A second minor peak on chromosome 4 from the West Africa study (LOD 1.37, 125 cM) also overlapped with a peak on chromosome 4 (135 cM; LOD 2.26) in our study.…”

Section: Discussionmentioning

confidence: 56%

“…Sale et al (8) examined 392 microsatellite markers in 675 individuals (638 affected sibpairs) and reported suggestive linkage on chromosome 6 near D6S1035 (163.5 cM); other regions on 7p showed an association with earliest onset diabetes. Rotimi et al (9) examined 390 microsatellite markers in 691 individuals (343 affected sibpairs) from West Africa and found evidence for linkage on chromosomes 20q13.3 and 12q24. Studies of single nucleotide polymorphism (SNP)-based linkage scans have not been published.…”

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confidence: 99%

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Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort

et al. 2009

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OBJECTIVE— We used a single nucleotide polymorphism (SNP) map in a large cohort of 580 African American families to identify regions linked to type 2 diabetes, age of type 2 diabetes diagnosis, and BMI. RESEARCH DESIGN AND METHODS— After removing outliers and problematic samples, we conducted linkage analysis using 5,914 SNPs in 1,344 individuals from 530 families. Linkage analysis was conducted using variance components for type 2 diabetes, age of type 2 diabetes diagnosis, and BMI and nonparametric linkage analyses. Ordered subset analyses were conducted ranking on age of type 2 diabetes diagnosis, BMI, waist circumference, waist-to-hip ratio, and amount of European admixture. Admixture mapping was conducted using 4,486 markers not in linkage disequilibrium. RESULTS— The strongest signal for type 2 diabetes (logarithm of odds [LOD] 4.53) was a broad peak on chromosome 2, with weaker linkage to age of type 2 diabetes diagnosis (LOD 1.82). Type 2 diabetes and age of type 2 diabetes diagnosis were linked to chromosome 13p (3–22 cM; LOD 2.42 and 2.46, respectively). Age of type 2 diabetes diagnosis was linked to 18p (66 cM; LOD 2.96). We replicated previous reports on chromosome 7p (79 cM; LOD 2.93). Ordered subset analysis did not overlap with linkage of unselected families. The best admixture score was on chromosome 12 (90 cM; P = 0.0003). CONCLUSIONS— The linkage regions on chromosomes 7 (27–78 cM) and 18p overlap prior reports, whereas regions on 2p and 13p linkage are novel. Among potential candidate genes implicated are TCF7L1 , VAMP5, VAMP8, CDK8 , INSIG2 , IPF1 , PAX8 , IL18R1 , members of the IL1 and IL1 receptor families, and MAP4K4 . These studies provide a complementary approach to genome-wide association scans to identify causative genes for African American diabetes.

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Section: Discussionmentioning

confidence: 56%

mentioning

confidence: 99%

Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort

et al. 2009

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“…Studies of mitochondrial and Y-chromosomal markers have determined that the genetic distance between the Gullah and Sierra Leonean tribes (Mende, Temne, etc.) is quite short and measurably shorter than other African American populations (8 -10); thus, studyspecific loci may represent ancestral differences between the Gullah and the Ghanaian and Nigerian families of the Africa America Diabetes Mellitus study (3). Interestingly, the region of chromosome 10 containing the transcription factor 7-like 2 (TCF7L2) gene-shown to be important in populations with African ancestry (32-34)-did not produce evidence for linkage in this population.…”

Section: Discussionmentioning

confidence: 92%

“…To date, there have been only three reported linkage scans for type 2 diabetes in populations of African descent: two in African Americans (1,2) and one in African families from Ghana and Nigeria (3). Although there have been several recent genome-wide association studies (GWASs) conducted in primarily European populations, none has been reported for African Americans, and relatively few diabetes genes have been found in African American populations using candidate gene approaches (4).…”

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confidence: 99%

Genome-Wide Linkage Scan in Gullah-Speaking African American Families With Type 2 Diabetes

Sale

Lu²,

Spruill³

et al. 2009

Diabetes

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OBJECTIVE— The Gullah-speaking African American population from the Sea Islands of South Carolina is characterized by a low degree of European admixture and high rates of type 2 diabetes and diabetic complications. Affected relative pairs with type 2 diabetes were recruited through the Sea Islands Genetic African American Registry (Project SuGAR). RESEARCH DESIGN AND METHODS— We conducted a genome-wide linkage scan, genotyping 5,974 single nucleotide polymorphisms in 471 affected subjects and 50 unaffected relatives from 197 pedigrees. Data were analyzed using a multipoint engine for rapid likelihood inference and ordered subsets analyses (OSAs) for age at type 2 diabetes diagnosis, waist circumference, waist-to-hip ratio, and BMI. We searched for heterogeneity and interactions using a conditional logistic regression likelihood approach. RESULTS— Linkage peaks on chromosome 14 at 123–124 cM were detected for type 2 diabetes (logarithm of odds [LOD] 2.10) and for the subset with later age at type 2 diabetes diagnosis (maximum LOD 4.05). Two linkage peaks on chromosome 7 were detected at 44–45 cM for type 2 diabetes (LOD 1.18) and at 78 cM for type 2 diabetes (LOD 1.64) and the subset with earlier age at type 2 diabetes diagnosis (maximum LOD 3.93). The chromosome 14 locus and a peak on 7p at 29.5 cM were identified as important in the multilocus model. Other regions that provided modest evidence for linkage included chromosome 1 at 167.5 cM (LOD 1.51) and chromosome 3 at 121.0 cM (LOD 1.61). CONCLUSIONS— This study revealed a novel type 2 diabetes locus in an African American population on 14q that appears to reduce age of disease onset and confirmed two loci on chromosome 7.

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“…Linkage studies for type 2 diabetes have provided promising and replicated findings on 1q21-q23 1,2 and 20q13. [3][4][5][6][7] These robust replications suggested the plausibility of localization of single or multiple susceptibility genes on these chromosomal regions. Subsequently, several studies performed fine mapping of these candidate regions but yielded little success.…”

Section: Introductionmentioning

confidence: 91%

Common variants of SLAMF1 and ITLN1 on 1q21 are associated with type 2 diabetes in Indian population

et al. 2012

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A Genome-Wide Search for Type 2 Diabetes Susceptibility Genes in West Africans

Abstract: The incidence of type 2 diabetes is growing rapidly, not only in developed countries but also worldwide. We chose to study type 2 diabetes in West Africa, where diabetes is less common than in the U.

Cited by 93 publications

References 21 publications

Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort

Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort

Genome-Wide Linkage Scan in Gullah-Speaking African American Families With Type 2 Diabetes

Common variants of SLAMF1 and ITLN1 on 1q21 are associated with type 2 diabetes in Indian population

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