Biomedical subjects

D C Rao

Publications and source records attributed to D C Rao.

At least 55 records · Page 3Linked to original sources

PubMed2004

Evidence of QTLs on chromosomes 1q42 and 8q24 for LDL-cholesterol and apoB levels in the HERITAGE family study.

Genome-wide multipoint linkage analyses were performed to identify chromosomal regions harboring genes influencing LDL-cholesterol, total apolipoprotein B (apoB), and LDL-apoB levels using 654 markers. They were assessed in a sedentary state (baseline) and after a 20 week endurance training program. Strong evidence for two quantitative trait loci (QTLs) for baseline levels was found. There is linkage evidence in black families on chromosomes 1q41-q44 [at marker D1S2860, 238 centimorgan (cM), with a maximum log of the odds (LOD) score of 3.7 for LDL-apoB] and in white families on chromosome 8q24 (at marker D8S1774, 142 cM, with LOD scores of 3.6, 3.3, and 2.5 for baseline LDL-cholesterol, LDL-apoB, and apoB, respectively). There were no strong signals for the lipoprotein training responses (as computed as the difference in posttraining minus baseline levels). In conclusion, QTLs for baseline apoB and LDL-cholesterol levels on chromosomes 1q41-q44 (in blacks) and 8q24 (in whites) were found. As there are no known strong candidate genes in these regions for lipids, follow-up studies to determine the source of those signals are needed.

Apolipoproteins B↗

PubMed2004

Compendium of genome-wide scans of lipid-related phenotypes: adding a new genome-wide search of apolipoprotein levels.

The genetic dissection of complex inherited diseases is a major challenge. Despite limited success in finding genes, substantial data based on genome-wide scan strategies is now available for a variety of diseases and related phenotypes. This can perhaps best be appreciated in the field of lipid and lipoprotein levels, where the amount of information generated is becoming overwhelming. We have created a database containing the results from whole-genome scans of lipid-related phenotypes undertaken to date. The usefulness of this database is demonstrated by performing a new autosomal genomic scan on apolipoprotein B (apoB), LDL-apoB, and apoA-I levels, measured in 679 subjects of 243 nuclear families. Linkage was tested using both allele-sharing and variance-component methods. Only two loci provided support for linkage with both methods: a LDL-apoB locus on 18q21.32 and an apoA-I locus on 3p25.2. Adding those findings to the database highlighted the fact that the former is reported as a lipid-related locus for the first time, whereas the latter has been observed before. However, concerns arise when displaying all data on the same map, because a large portion of the genome is now covered with loci supported by at least suggestive evidence of linkage.

Adult↗

PubMed2004

Differences in left ventricular structure between black and white hypertensive adults: the Hypertension Genetic Epidemiology Network study.

The degree to which ethnic differences in left ventricular structure among hypertensive adults are independent of clinical and hemodynamic factors remains uncertain. We assessed whether left ventricular mass and geometry differ between black and white hypertensives after accounting for differences in such factors. Our study group comprised 1060 black and 580 white hypertensive participants free of valvular or coronary disease in a population-based cohort. Blood pressure was measured during a clinic visit and echocardiography was performed using standardized protocols. After controlling for clinical and hemodynamic parameters (cardiac index, peripheral resistance index, and pulse pressure/stroke index), both left ventricular mass and relative wall thickness were higher in blacks than whites (173.9+/-30.9 versus 168.3+/-24.3 grams, P=0.006, and 0.355+/-0.055 versus 0.340+/-0.055 grams, P<0.001). Similarly, the adjusted risk of having left ventricular hypertrophy, whether indexed by height(2.7) or by body surface area, was greater for blacks than for whites (odds ratio: 1.80; 95% CI: 1.29 to 2.51; and odds ratio: 2.50; 95% CI: 1.58 to 3.96, respectively), and this was also true for concentric geometry (odds ratio: 2.28; 95% CI: 1.22 to 4.25). Further adjustment for relatedness in this genetic epidemiological study did not attenuate these differences. Our findings confirm the strong association between black ethnicity and increased left ventricular mass and relative wall thickness in hypertensive adults and demonstrate that these differences are independent of standard clinical and hemodynamic parameters. Whether such differences relate to distinct ambulatory pressure profiles or an ethnic propensity to cardiac hypertrophy requires further investigation.

Adult↗

PubMed2004

Acetylcholinesterase/paraoxonase genotype and expression predict anxiety scores in Health, Risk Factors, Exercise Training, and Genetics study.

Anxiety involves complex, incompletely understood interactions of genomic, environmental, and experience-derived factors, and is currently being measured by psychological criteria. Here, we report previously nonperceived interrelationships between expression variations and nucleotide polymorphisms of the chromosome 7q21-22 acetylcholinesterase-paraoxonase 1 (ACHE-PON1) locus with the trait- and state-anxiety measures of 461 healthy subjects from the Health, Risk Factors, Exercise Training, and Genetics Family Study. The AChE protein controls the termination of the stress-enhanced acetylcholine signaling, whereas the PON protein displays peroxidase-like activity, thus protecting blood proteins from oxidative stress damages. Serum AChE and PON enzyme activities were both found to be affected by demographic parameters, and showed inverse, reciprocal associations with anxiety measures. Moreover, the transient scores of state anxiety and the susceptibility score of trait anxiety both appeared to be linked to enzyme activities. This finding supported the notion of corresponding gene expression relationships. Parallel polymorphisms in the ACHE and PON1 genes displayed apparent associations with both trait- and state-anxiety scores. Our findings indicate that a significant source of anxiety feelings involves inherited and acquired parameters of acetylcholine regulation that can be readily quantified, which can help explaining part of the human variance for state and trait anxiety.

Acetylcholinesterase↗

PubMed2004

Quantitative trait loci for maximal exercise capacity phenotypes and their responses to training in the HERITAGE Family Study.

The purpose of this study was to identify regions of the human genome linked to maximal oxygen uptake (VO2max) and maximal power output (MPO), and their response to a standardized 20-wk endurance-training program in sedentary black and white subjects. A total of 509 polymorphic markers covering the 22 autosomes were used in the genome-wide linkage scan. Baseline phenotypes were adjusted for age, sex, and body mass, whereas the training responses were adjusted for age, sex, and the baseline values. Regression-based single- and multipoint linkage analyses were used. In the sedentary state, a total of 351 and 102 sibling pairs were available for whites and blacks, respectively, and 329 and 90 sibling pairs, respectively, for the training response phenotypes. Baseline VO2max showed promising linkage (P < 0.0023) with 11p15.1 (whites), and suggestive evidence of linkage (0.01 > P > 0.0023) was found on 1p31, 7q32, and 7q36 (blacks). Baseline MPO exhibited promising linkage on 10q23 and suggestive evidence of linkage on 13q33 and 18q11-q12 (whites). VO2max training response yielded promising linkages with markers on 1p31 (blacks) and suggestive on 4q27, 7q34, and 13q12 (whites) and on 16q22 and 20q13.1 (blacks). Training-induced changes in MPO showed promising linkages on 5q23 (whites) and suggestive on 1q21, 4p15.1, and 4p13 (whites) and on 1q22 and 13q11 (blacks). In conclusion, the strongest evidence of linkage was found on chromosomal regions 11p15 and 10q23 for VO2 max and MPO in the sedentary state and on chromosomes 1p31 and 5q23 for their responsiveness to training. These chromosomal regions harbor several candidate genes that deserve further investigation.

Adult↗

PubMed2004

Genetic association mapping under founder heterogeneity via weighted haplotype similarity analysis in candidate genes.

Taking advantage of increasingly available high-density single nucleotide polymorphism (SNP) markers within genes and across genomes, more and more genetic association studies began to use multiple closely linked markers in candidate genes. A practical analytical challenge arising in such studies is the possibility that not all case chromosomes have inherited disease-causing mutations from a common ancestral chromosome (founder heterogeneity). To alleviate the problem, we propose a method that applies a clustering algorithm to haplotype similarity analysis. The method identifies a sequence of nested subsets of case chromosomes by a peeling procedure, where each subset is relatively homogeneous. The average similarity score estimated from each subset in the sequence is compared to that estimated in controls, and a raw (unadjusted for multiple comparisons) P value is obtained. The test for the association between the trait and the candidate gene is based on the minimum raw P value observed in the comparison sequence, with its significance level estimated by a permutation procedure. The method can be applied to both haplotype and genotype data. Simulation studies suggest that our method has the correct type I error rate, and is generally more powerful than existing methods of haplotype similarity analysis.

Alleles↗

PubMed2004

Association of inappropriate left ventricular mass with systolic and diastolic dysfunction: the HyperGEN study.

BACKGROUND: Left ventricular mass (LVM) exceeding values appropriate for individual workload is associated with concentric LV geometry and systolic dysfunction at both the midwall and chamber levels, even independently of clearcut LV hypertrophy, and is a marker of adverse prognosis. No information is available on whether inappropriate LVM is associated with alterations of LV diastolic properties in unselected population-based studies. METHODS: We examined 1513 hypertensive participants from the HyperGEN population who were without prevalent cardiovascular disease. The LVM prediction from stroke work (systolic blood pressure x Doppler stroke volume), sex, and height (in meters2.7) was derived in 210 nonobese, normal individuals. Observed/predicted LVM >133% defined inappropriate LVM. RESULTS: Participants with inappropriate LVM (229 subjects [15%]) exhibited higher LV dimensions and relative wall thickness, lower ejection fraction, midwall shortening and cardiac output, and prolonged isovolumic relaxation time (IVRT; P < or = .001). Other diastolic abnormalities were not associated with inappropriate LVM. After accounting for demographic and hemodynamic confounders, IVRT was directly related to excess LVM, whereas deceleration time of E velocity was negatively related to excess LVM. Nonechocardiographic correlates of prolonged relaxation included aging, African American ethnicity, male gender, and diabetes. CONCLUSIONS: The LVM exceeding the compensatory needs for workload is associated with delayed LV relaxation as well as mild midwall and chamber systolic dysfunction, independently of demographic, clinical, and hemodynamic confounders. Inappropriately high LVM also correlates with features of increased myocardial stiffness, coexisting with evidence of prolonged LV relaxation.

Adult↗

PubMed2004

Association of apolipoprotein E polymorphism with blood lipids and maximal oxygen uptake in the sedentary state and after exercise training in the HERITAGE family study.

The relationship of apolipoprotein E (apo E) genotypes to plasma lipid and maximal oxygen uptake (Vo(2max)) was studied in the sedentary state and after a supervised exercise training program in black and white men and women. At baseline, the apo E 2/3 genotype was associated with the lowest, and apo E 3/4 and E4/4 with the highest low-density liporpotein (LDL) cholesterol and apo B levels in men and women of both races, while female (not male) carriers of apo E3 had higher high-density lipoprotein (HDL) cholesterol levels than carriers of other genotypes. Very-low-density lipoprotein (VLDL) cholesterol and triglyceride levels were significantly higher in carriers of both apo E2 and apo E4 in white men only. Racial and sex differences were noted in lipid responses to exercise training across genotypes with a significantly greater increase in HDL cholesterol observed only in white female carriers of apo E 2/3 and E3/3, as compared to apo E4/4. Apo E polymorphism was not found to be associated with Vo(2max) levels either in the sedentary state nor the Vo(2max) response to exercise training, contrary to previous reports.

Alleles↗

PubMed2004

Fitness alters the associations of BMI and waist circumference with total and abdominal fat.

OBJECTIVE: We tested the following hypotheses in black and white men and women: 1) for a given BMI or waist circumference (WC), individuals with moderate cardiorespiratory fitness (CRF) have lower amounts of total fat mass and abdominal subcutaneous and visceral fat compared with individuals with low CRF; and 2) exercise training is associated with significant reductions in total adiposity and abdominal fat independent of changes in BMI or WC. RESEARCH METHODS AND PROCEDURES: The sample included 366 sedentary male (111 blacks and 255 whites) and 462 sedentary female (203 blacks and 259 whites) participants in the HERITAGE Family Study. The relationships between BMI and WC with total fat mass (determined by underwater weighing) and abdominal subcutaneous and visceral fat (determined by computed tomography) were compared in subjects with low (lower 50%) and moderate (upper 50%) CRF. The effects of a 20-week aerobic exercise training program on changes in these adiposity variables were examined in 86% of the subjects. RESULTS: Individuals with moderate CRF had lower levels of total fat mass and abdominal subcutaneous and visceral fat than individuals with low CRF for a given BMI or WC value. The 20-week aerobic exercise program was associated with significant reductions in total adiposity and abdominal fat, even after controlling for reductions in BMI and WC. With few exceptions, these observations were true for both men and women and blacks and whites. DISCUSSION: These findings suggest that a reduction in total adiposity and abdominal fat may be a means by which CRF attenuates the health risk attributable to obesity as determined by BMI and WC.

Abdomen↗

PubMed2004

Sex differences in the relationships of abdominal fat to cardiovascular disease risk among normal-weight white subjects.

The objectives of this study are to investigate the relationships between abdominal fat and risk factors for cardiovascular disease (CVD) among normal-weight (NW) white subjects and to determine how these relationships differ by sex. NW adults (177 males and 258 females) and overweight adults (133 males and 111 females) from the Québec Family Study and the HERITAGE Family Study were retained for this study. Risk factors included systolic and diastolic blood pressures, low-density lipoprotein and high-density lipoprotein cholesterols, triglycerides, and fasting glucose. Only in NW female adults, abdominal visceral fat (AVF) area assessed by computed tomography was significantly correlated with all risk factors, except for fasting glucose, even after age, study cohort, and fat mass were taken into account. NW female subjects with at least one risk factor had a significantly higher AVF than those without risk factors, although the difference was small. Thus, only NW female adults with more AVF tended to have a more adverse CVD risk factor profile.

Abdomen↗

PubMed2004

Generalized abdominal visceral fat prediction models for black and white adults aged 17-65 y: the HERITAGE Family Study.

OBJECTIVE: To determine if the relationship between abdominal visceral fat (AVF) and measures of adiposity are different between Black and White subjects and to develop valid field prediction models that accurately identify those individuals with AVF levels associated with high risk for chronic disease. DESIGN: Cross-sectional measurements obtained from 91 Black men, 137 Black women, 227 White men, and 237 White women subjects, ages 17-65 y, who were participants in the HERITAGE Family Study, both at baseline and following 20 weeks of endurance training. MEASUREMENTS: AVF, abdominal subcutaneous fat (ASF), abdominal total fat (ATF), and sagittal diameter (SagD) were measured by computed tomography (CT). Body density was determined by hydrostatic weighing and was used to estimate relative body fat. Arm, waist (WC), and hip circumferences and skinfold thickness measures were taken, and BMI was calculated from weight (kg) and height (m(2)). Since CT abdominal fat variables were skewed, a natural log transformation (Ln) was used to produce a normal distribution. The General Linear Model (GLM) procedure was used to test the relationship between AVF and two different groups of variables-CT and anthropometric. RESULTS: The AVF of White men and women was significantly higher than that of Black men and women, independent of BMI, WHR, WC, and age, and was greater for men than for women. The CT model showed that the combination of SagD, Ln (ASF), age, and race accounted for 84 and 75% of the variance in AVF in men and women, respectively. The anthropometric model provided two valid generalized field AVF prediction equations. The Field-I equation, which included BMI, WHR, age and race, had an r(2) of 0.78 and 0.73 for men and women, respectively. The Field-II equation, which included BMI (women only), WC, age, and race, had an r(2) of 0.78 and 0.72 for men and women, respectively. The field model equations became less accurate as the estimated AVF increased. CONCLUSIONS: (1) At the same age and level of adiposity, Black men and women have less AVF than White men and women. These differences are greater in men than in women. (2) The field regression equations can be generalized to the diverse group of adults studied, both in an untrained and trained state. However, their accuracy decreases with increasing levels of AVF.

Abdomen↗

PubMed2004

A genome-wide linkage scan for dietary energy and nutrient intakes: the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study.

BACKGROUND: A poor diet is a risk factor for chronic diseases such as obesity, cardiovascular disease, hypertension, and some cancers. Twin and family studies suggest that genetic factors potentially influence energy and nutrient intakes. OBJECTIVE: We sought to identify genomic regions harboring genes affecting total energy, carbohydrate, protein, and fat intakes. DESIGN: We performed a genomic scan in 347 white sibling pairs and 99 black sibling pairs. Dietary energy and nutrient intakes were assessed by using Willett's food-frequency questionnaire. Single-point and multipoint Haseman-Elston regression techniques were used to test for linkage. These subjects were part of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, a multicenter project undertaken by 5 laboratories. RESULTS: In the whites, the strongest evidence of linkage appeared for dietary energy and nutrient intakes on chromosomes 1p21.2 (P = 0.0002) and 20q13.13 (P = 0.00007), and that for fat intake appeared on chromosome 12q14.1 (P = 0.0013). The linkage evidence on chromosomes 1 and 20 related to total energy intake rather than to the intake of specific macronutrients. In the blacks, promising linkages for macronutrient intakes occurred on chromosomes 12q23-q24.21, 1q32.1, and 7q11.1. Several potential candidate genes are encoded in and around the linkage regions on chromosomes 1p21.2, 12q14.1, and 20q13.13. CONCLUSIONS: These are the first reported human quantitative trait loci for dietary energy and macronutrient intakes. Further study may refine these quantitative trait loci to identify potential candidate genes for energy and specific macronutrient intakes that would be amenable to more detailed molecular studies.

Adolescent↗

PubMed2004

Neuromedin beta: a strong candidate gene linking eating behaviors and susceptibility to obesity.

BACKGROUND: Obesity is frequently associated with eating disorders, and evidence indicates that both conditions are influenced by genetic factors. However, little is known about the genes influencing eating behaviors. OBJECTIVE: The objective was to identify genes associated with eating behaviors. DESIGN: Three eating behaviors were assessed in 660 adults from the Quebec Family Study with the use of the Three-Factor Eating Questionnaire. A genome-wide scan was conducted with a total of 471 genetic markers spanning the 22 autosomes to identify quantitative trait loci for eating behaviors. Body composition and macronutrient and energy intakes were also measured. RESULTS: Four quantitative trait loci were identified for disinhibition and susceptibility to hunger. Of these, the best evidence of linkage was found between a locus on chromosome 15q24-q25 and disinhibition (P <0.0058) and susceptibility to hunger (P <0.0001). After fine-mapping, the peak linkage was found between markers D15S206 and D15S201 surrounding the neuromedin beta (NMB) gene. A missense mutation (p.P73T) located within the NMB gene showed significant associations with eating behaviors and obesity phenotypes. The T73T homozygotes were 2 times as likely to exhibit high levels of disinhibition (odds ratio: 1.8; 95% CI: 1.07, 2.89; P=0.03) and susceptibility to hunger (odds ratio: 1.9; 95% CI: 1.15, 3.06; P=0.01) as were the P73 allele carriers. Six-year follow-up data showed that the amount of body fat gain over time in T73T subjects was >2 times that than in P73P homozygotes (3.6 compared with 1.5 kg; P <0.05). CONCLUSION: The results suggest that NMB is a very strong candidate gene of eating behaviors and predisposition to obesity.

Adult↗

PubMed2004

Calcium intake is associated with adiposity in Black and White men and White women of the HERITAGE Family Study.

Calcium (Ca(2+)) intake may play a role in the regulation of body weight. Increased Ca(2+) intake has been associated with lower body weight, BMI, and adiposity measures in cross-sectional studies. We examined the association between Ca(2+) intake, derived from the Willett FFQ, and overall and abdominal adiposity in Black and White men and women of the HERITAGE Family Study. BMI, the percentage of body fat (%FAT), the sum of 8 skinfold thicknesses, computerized tomography total abdominal fat (TAF), abdominal visceral (AVF) and abdominal subcutaneous (ASF) fat, and waist circumference were measured in 362 men (109 Blacks, 253 Whites) and 462 women (201 Blacks, 261 Whites). Subjects were divided into tertiles of energy-adjusted Ca(2+) intake. Adiposity measures across tertiles were compared by ANOVA and also regressed against the energy-adjusted Ca(2+) intake to test for a linear trend. The strongest inverse associations appeared in Black men and White women. Black men in the high Ca(2+) intake group were leaner than those in the low Ca(2+) intake group: BMI 23.4 +/- 0.9 vs. 26.7 +/- 1.1 kg/m(2) (P = 0.01); for all other adiposity measures, P < 0.05. In White women, regression analyses showed significant inverse associations between Ca(2+) intake and BMI (P = 0.02), %FAT (P = 0.001), TAF (P = 0.006), AVF (P = 0.03), and ASF (P = 0.01). The percentage of fat of White men in the highest Ca(2+) intake group was significantly lower than in the lowest Ca(2+) group (P = 0.04). No significant associations were found in Black women. Low Ca(2+) intake may be associated with higher adiposity, particularly in men and White women.

Adipose Tissue↗

PubMed2004

Functional dimorphism of two hAgRP promoter SNPs in linkage disequilibrium.

The agouti related protein (AgRP) exerts its anabolic effects on food intake by antagonising the alpha-melanocyte stimulating hormone (alpha-MSH) at its receptors, melanocortin receptors 3 and 4 (MC3R and MC4R). A single nucleotide polymorphism (SNP) in the promoter of the human AgRP (hAgRP), -38C>T, was associated with low body fatness. The -38T allele that was associated with low body fatness also resulted in lower promoter activity. Here we report a novel SNP, -3019G>A, again in the promoter of hAgRP, which is in complete linkage disequilibrium (LD) with the -38C>T SNP (linked alleles: -3019A/-38T and -3019G/-38C). Functional analyses in a human adrenal and two mouse hypothalamus cell lines showed that the -3019A allele had significantly higher promoter activity. Hence, the two linked alleles (-3019A and -38T) had opposite effects on promoter function and yet they were both associated with low body fatness. The region encompassing the -38C>T SNP had approximately 1000-fold higher activity than the region encompassing the -3019G>A SNP, potentially determining the net functional effect between these two SNPs.

Agouti-Related Protein↗

PubMed2004

Power loss for linkage analysis due to the dichotomization of trichotomous phenotypes.

OBJECTIVES: Some traits, while naturally polychotomous, are routinely dichotomized for genetic analysis. Dichotomization, intuitively, leads to a loss of power to detect linkage, as some phenotypic variability is discarded. This paper examines this power loss in the context of a trichotomous trait. METHODS: To examine this power loss, we performed a simulation study where a trichotomous trait was simulated in a sample of 1,000 sib-pairs under various genetic models. The study was replicated 1,000 times. Linkage analysis using a variance components method, as implemented in Mx, was then performed on the trichotomous trait and compared with that on a dichotomized version of the trait. RESULTS: A comparison of the power and false positive rates of the analyses shows that power to detect linkage was increased by up to 22 percentage points simply by examining the trait as a trichotomy instead of a dichotomy. Under all models examined, the trichotomous analysis outperformed the dichotomous version. CONCLUSIONS: Comparable levels of false positive rates under both methods confirm that this power gain comes solely from the information lost upon dichotomization. Thus, dichotomizing tri- or poly-chotomous traits can lead to crippling power loss, especially in the case of many loci of small effect.

Alleles↗

PubMed2004

Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis in response to regular exercise in nondiabetic individuals: the HERITAGE family study.

We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. Similar interaction was observed in blacks (P = 0.046). Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals.

Adult↗

PubMed2003

Genome-wide linkage scan reveals multiple susceptibility loci influencing lipid and lipoprotein levels in the Quebec Family Study.

A genome-wide linkage study was performed to identify chromosomal regions harboring genes influencing lipid and lipoprotein levels. Linkage analyses were conducted for four quantitative lipoprotein/lipid traits, i.e., total cholesterol, triglyceride, HDL-cholesterol (HDL-C), and LDL-C concentrations, in 930 subjects enrolled in the Québec Family Study. A maximum of 534 pairs of siblings from 292 nuclear families were available. Linkage was tested using both allele-sharing and variance-component linkage methods. The strongest evidence of linkage was found on chromosome 12q14.1 at marker D12S334 for HDL-C, with a logarithm of the odds (LOD) score of 4.06. Chromosomal regions harboring quantitative trait loci (QTLs) for LDL-C included 1q43 (LOD = 2.50), 11q23.2 (LOD = 3.22), 15q26.1 (LOD = 3.11), and 19q13.32 (LOD = 3.59). In the case of triglycerides, three markers located on 2p14, 11p13, and 11q24.1 provided suggestive evidence of linkage (LOD > 1.75). Tests for total cholesterol levels yielded significant evidence of linkage at 15q26.1 and 18q22.3 with the allele-sharing linkage method, but the results were nonsignificant with the variance-component method. In conclusion, this genome scan provides evidence for several QTLs influencing lipid and lipoprotein levels. Promising candidate genes were located in the vicinity of the genomic regions showing evidence of linkage.

Adult↗