The genetic architecture of lipoprotein subclasses in Gullah-speaking African American families enriched for type 2 diabetes: The Sea Islands Genetic African American Registry (Project SuGAR)

Abstract

This article is available online at http://www.jlr.org studied in this sample and that novel loci on chromosomes 6, 10, 16, and 20 may harbor genes contributing to small, atherogenic LDL particle concentration and large, triglyceride-rich VLDL particle concentration. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among individuals with diabetes ( 1-3 ). For example, the risk of coronary heart disease is 2-4 times higher in diabetic patients compared with nondiabetic individuals ( 4-8 ). Dyslipidemia is thought to be a potential common link between these two conditions ( 9, 10 ). The principal lipoprotein classes, VLDL, LDL, and HDL, have received considerable attention as cardiovascular disease risk factors in the epidemiology literature. Several genes have also been reported to be associated with these lipoprotein phenotypes ( 11-13 ). In fact, genetic correlation and genes with possible pleiotropic effect on LDL, Abstract We sought to partition the genetic and environmental infl uences on lipoprotein subclasses and identify genomic regions that may harbor genetic variants that infl uence serum lipoprotein levels in a sample of Gullah-speaking African-Americans. We genotyped 5,974 SNPs in 979 subjects from 418 pedigrees and used the variance component approach to compute heritability estimates, genetic and environmental correlations, and linkage analyses for selected lipoprotein subclasses. The highest heritability estimate was observed for large VLDL particle concentration (0.56 ± 0.14). Mean LDL particle size and small LDL particle concentration ( ؊ 0.94) had the strongest genetic correlation estimate. The highest logarithm of odds (LOD) score detected (3.0) was on chromosome 6p24 for small LDL particle concentration. The strongest signal, obtained with the reduced sample of diabetic individuals only, was observed on chromosome 20p13 for small LDL particle concentration. The highest bivariate linkage signal (LOD 2.4) was observed on chromosome 6p24 for mean LDL particle size and small LDL particle concentration.jlr Our results suggest a significant genetic contribution to multiple lipoprotein subclasses

Quantitative genetic analyses of postcanine morphological crown variation

“…How patterns of mtDNA or Y chromosome haplotype diversity map onto dental phenotypes is difficult to predict. We note, however, that previous quantitative genetic studies of Gullah biomedical data failed to find evidence of bias due to population structure (Divers et al, ). Thus, there is no clear rationale for assuming a causal relationship between the isolation and endogamy of the Gullah and the low heritability estimates reported here and in our previous articles.…”

Plasma Metabolomic Profiles Reflective of Glucose Homeostasis in Non-Diabetic and Type 2 Diabetic Obese African-American Women

“…Briefly, archived plasma samples derived from body mass index- (BMI) and age-matched overweight to obese type 2 diabetic (n = 44) and non-diabetic (n = 12) Gullah-speaking African-American women with or without a UCP3 g/a missense polymorphism were evaluated. Volunteers were recruited as part of the Project SuGAR study described in detail elsewhere [28] – [31] . Considering that this group is of a single sex, displays an extraordinarly low genetic admixture, lives in a relatively small geographical space, and has a common dietary intake pattern, we anticipate that the cohort is well-suited for metabolomics studies since biological metabolite signal-to-noise should be low.…”

Co‐shared genetics and possible risk gene pathway partially explain the comorbidity of schizophrenia, major depressive disorder, type 2 diabetes, and metabolic syndrome

“…However, as described above, PRL /6p22.3, PRLR /5p13.2, PRLHR/ 10q26.13, OXT / 20p13, OXTR /3p25, and NPY /7p15.1 genes/loci have all been variably linked and/or associated with prediabetes traits, SCZ, bipolar disorder, MDD, postpartum depression, T2D, C‐reactive protein, T2D‐atherogenic particles, MetS, and CAD (An et al, ; Bespalova et al, ; Bosse et al, ; Bowden et al, ; Breen et al, ; K. Bulayeva et al, ; Divers et al, ; Fallin et al, ; Fanous et al, ; Ghosh et al, ; Gornick et al, ; Jonas et al, ; Kong et al, ; Lakka et al, ; Lu et al, ; Marcheco‐Teruel et al, ; Maziade et al, ; Montag et al, ; Myers et al, ; Nilsson et al, ; Rybakowski et al, ; Smith et al, ; Teltsh et al, ; Teltsh et al, ; Voight et al, ; Y. Wang et al, ; Wiltshire et al, ; Zeggini et al, ; Zintzaras & Ioannidis, ). Furthermore, the PRL , PRLR , PRLHR , OXT , OXTR , and NPY genes play a key role in the PRL‐pathway and may, if impaired, confer risk for T2D, Mets, associated traits, and the SCZ‐T2D and/or ‐MetS comorbidity.…”

“…OXT lies on 20p13, a locus linked and/or associated with small atherogenic LDL‐particles, large VLDL‐particles in diabetic subjects (Divers et al, ), T2D (Ghosh et al, ), MDD (K. Bulayeva et al, ), and SCZ (Fanous et al, ; Teltsh et al, ; Teltsh et al, ). OXT is not associated with childhood depression (Strauss et al, ) and is associated with postpartum depression (Jonas et al, ) and SCZ (Montag et al, ; Teltsh et al, ).…”