A genome-wide scan for quantitative trait loci linked to obesity phenotypes among West Africans

Chen, G; Adeyemo, Adebowale; Johnson, Thomas; Zhou, Jie; Amoah, Albert; Owusu, Samuel; Acheampong, Joseph; Agyenim-Boateng, Kofi; Eghan, Benjamin; Oli, Johnnie; Okafor, Godfrey; Abbiyesuku, F M; Dunston, Georgia M.; Chen, Y; Collins, Francis S.; Rotimi, Charles N.

doi:10.1038/sj.ijo.0802873

Cited by 30 publications

(25 citation statements)

References 22 publications

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“…Genome-wide linkage analyses of obesity-related phentoypes have indicated strong linkage to chromosomes 1, 2, 5, 7, 8, and 11 in West Africans (4,29). These results demonstrate that multiple loci, together with environmental factors, likely contribute to the phenotypic variance of obesity-related traits.…”

Section: Obesitymentioning

confidence: 73%

African Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

Campbell

Tishkoff

2008

Annu. Rev. Genom. Hum. Genet.

661

573

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Comparative studies of ethnically diverse human populations, particularly in Africa, are important for reconstructing human evolutionary history and for understanding the genetic basis of phenotypic adaptation and complex disease. African populations are characterized by greater levels of genetic diversity, extensive population substructure, and less linkage disequilibrium (LD) among loci compared to non-African populations. Africans also possess a number of genetic adaptations that have evolved in response to diverse climates and diets, as well as exposure to infectious disease. This review summarizes patterns and the evolutionary origins of genetic diversity present in African populations, as well as their implications for the mapping of complex traits, including disease susceptibility.

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Section: Obesitymentioning

confidence: 73%

African Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

Campbell

Tishkoff

2008

Annu. Rev. Genom. Hum. Genet.

661

573

View full text Add to dashboard Cite

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“…In humans, loss-of-function mutations in PCSK1 cause monogenic obesity, impaired glucose tolerance and other related disorders. [4][5][6] In both genome-wide linkage studies [7][8][9][10] and candidate gene strategy studies, 11 single-nucleotide polymorphisms (SNPs) in the PCSK1 gene were associated with obesity. Most of these studies focused on the SNPs rs6232 and rs6235.…”

Section: Introductionmentioning

confidence: 99%

The obesity-related polymorphism PCSK1 rs6235 is associated with essential hypertension in the Han Chinese population

Ling

et al. 2012

Hypertens Res

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Proprotein convertase subtilisin/kexin-type 1 (PCSK1) is a prohormone convertase that has an important role in prohormone maturation including the process of prorenin to renin. We studied the association of the PCSK1 single-nucleotide polymorphism (SNP) rs6235 (encoding an S690T substitution) with essential hypertension (EH), obesity and related traits in the Han Chinese population. The rs6235 SNP in the PCSK1 gene was investigated using a case-control study design, with 1034 hypertension cases and 1112 normotensive controls. In this study, the rs6235 SNP was significantly associated with hypertension (OR ¼ 1.26, 95% CI (1.10-1.46), P ¼ 0.001); the odds ratios of GC vs GG and CC vs GG were 1.30 (95% CI (1.06-1.58), P ¼ 0.010) and 1.55 (95% CI (1.12-2.13), P ¼ 0.007), respectively. In the controls, the C-allele was associated with increased systolic (P ¼ 0.010) and diastolic (P ¼ 0.010) blood pressure levels. In all of the EH patients and EH patients without a history of renin-angiotensin-aldosterone (RAA) system-related antagonists, the C-allele was associated with increased plasma renin activity (P ¼ 0.00004 and 0.002, respectively) and aldosterone levels (P ¼ 0.018 and 0.005, respectively). The C-allele was also associated with increased body mass index (BMI) (P ¼ 0.010) in the normotensive controls. In conclusion, the PCSK1 SNP rs6235 was associated with EH and blood pressure in the Han Chinese population, and this association may be mediated by the SNP's effect on RAA levels. rs6235 was also associated with BMI in this population.

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“…Furthermore, 5q14 was detected for the broad phenotype in pair with 14q21. Chromosome 5q14 has previously been reported as linked to diabetes-related phenotypes such as body mass index, fat mass, and percent body fat (Chen et al 2005), and 14q21 has previously been suggested as linked to T2DM (Wiltshire et al 2004). …”

Section: Susceptibility Loci For Diabetes-related Traitsmentioning

confidence: 99%

Applying Novel Genome-Wide Linkage Strategies to Search for Loci Influencing Type 2 Diabetes and Adult Height in American Samoa

Åberg¹,

Sun²,

Smelser³

et al. 2008

Human Biology

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Type 2 diabetes mellitus (T2DM) is a common complex phenotype that by the year 2010 is predicted to affect 221 million people globally. In the present study we performed a genome-wide linkage scan using the allele-sharing statistic S all implemented in Allegro and a novel twodimensional genome-wide strategy implemented in Merloc that searches for pairwise interaction between genetic markers located on different chromosomes linked to T2DM. In addition, we used a robust score statistic from the newly developed QTL-ALL software to search for linkage to variation in adult height. The strategies were applied to a study sample consisting of 238 sib-pairs affected with T2DM from American Samoa. We did not detect any genome-wide significant susceptibility loci for T2DM. However, our two-dimensional linkage investigation detected several loci pairs of interest, including 11q22 and 21q21, 9q21 and 11q22, 1p22-p21 and 4p15, and 4p15 and 15q11-q14, with a two-loci maximum LOD score (MLS) greater than 2.00. Most detected individual loci have previously been identified as susceptibility loci for diabetes-related traits. Our two-dimensional linkage results may facilitate the selection of potential candidate genes and molecular pathways for further diabetes studies because these results, besides providing candidate loci, also demonstrate that polygenic effects may play an important role in T2DM. Linkage was detected (p value of 0.005) for variation in adult height on chromosome 9q31, which was reported previously in other populations. Our finding suggests that the 9q31 region may be a strong quantitative trait locus for adult height, which is likely to be of importance across populations. NIH Public Access Author ManuscriptHum Biol. Author manuscript; available in PMC 2013 July 04. DIABETES; STATURE; LINKAGE ANALYSIS; TWO-DIMENSIONAL LINKAGE; QUANTITATIVE TRAIT LOCUS; QTL-ALL SOFTWAREType 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by insulin resistance and dysfunction of the pancreatic beta cells. The disease results from a complex interaction of genetic and environmental factors and is strongly associated with obesity and modernized lifestyle. The disease has emerged to become a major public health problem. In 2000 T2DM affected 151 million people globally. This number is predicted to increase to 221 million in 2010, and the greatest proportional increase is expected to occur in regions adopting a modernized lifestyle, such as Africa and Asia with a 50% and 57% increase, respectively (Zimmet et al. 2001).A genetic contribution to the development of T2DM is supported by family aggregation with increased risk of developing the disease for first-degree relatives of probands and a greater concordance between affected monozygotic twins compared to dizygotic twins (Barroso 2005). In addition, disease prevalence varies substantially between ethnic groups living in the same environment, suggesting racial disparity for T2DM (Carulli et al. 2005).In this study we search for linkage to T2DM i...

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A genome-wide scan for quantitative trait loci linked to obesity phenotypes among West Africans

Cited by 30 publications

References 22 publications

African Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

African Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

The obesity-related polymorphism PCSK1 rs6235 is associated with essential hypertension in the Han Chinese population

Applying Novel Genome-Wide Linkage Strategies to Search for Loci Influencing Type 2 Diabetes and Adult Height in American Samoa

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