Genome-Wide Linkage Scan for Physical Activity Levels in the Quebec Family Study

Simonen, Riitta; Rankinen, Tuomo; Pérusse, Louis; Rice, Treva; Rao, D. C.; Chagnon, Yvon C.; Bouchard, Claude; Study, Quebec Family

doi:10.1249/01.mss.0000078937.22939.7e

Cited by 72 publications

(59 citation statements)

References 33 publications

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“…Strong evidence for linkage of plasma leptin levels, one of the most robust markers of fat mass, to this region of chromosome 2 was also seen in a genome-wide scan performed in French obese sibling pairs (6). Other studies have suggested a role for genes in this region in phenotypes such as serum triglycerides (17), blood pressure (18), physical inactivity (19), and type 2 diabetes (20). Association studies of the POMC gene and indexes of adiposity have been inconsistent (21,22), but most have been underpowered.…”

Section: Discussionmentioning

confidence: 75%

Heterozygosity for a POMC-Null Mutation and Increased Obesity Risk in Humans

Farooqi

Drop

Clements³

et al. 2006

Diabetes

209

132

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Congenital deficiency of proopiomelanocortin (POMC) results in a syndrome of hypoadrenalism, severe obesity, and altered skin and hair pigmentation. The concept that subtle variation in POMC expression and/or function might contribute to common obesity is suggested by studies reporting linkage of obesity-related traits to a locus on chromosome 2p22 encompassing the POMC gene. We identified a novel homozygous frameshift (C6906del) mutation in POMC in a child of Turkish origin with severe obesity and hypoadrenalism. This mutation would be predicted to lead to the loss of all POMC-derived peptides. The availability of a large extended pedigree provided the opportunity to address whether loss of one copy of the POMC gene was sufficient to alter obesity risk. Twelve relatives were heterozygous for the mutation and 7 were wild type. Of the heterozygotes, 11 of 12 heterozygotes were obese or overweight compared with only 1 of 7 of the wild-type relatives. The mean BMI SD score was 1.7 ؎ 0.5 in heterozygotes and 0.4 ؎ 0.4 in the wild-type relatives. Parametric linkage analysis of the trait "overweight" provided statistically significant evidence of linkage with this locus, with a maximum "location score" (comparable with multipoint logarithm of odds scores) of 3.191. We conclude that loss of one copy of the POMC gene predisposes to obesity in humans. Thus, genetic variants having relatively subtle effects on POMC expression and function could influence susceptibility to obesity. Diabetes 55:2549 -2553, 2006 P roopiomelanocortin (POMC) is a complex propeptide encoding a range of melanocortin peptides that are released by tissue-specific proteolytic processing (1). These peptides have important roles in a range of functions such as skin pigmentation and the control of adrenal growth and function (2). In the central nervous system, POMC is most highly expressed in the arcuate nucleus of the hypothalamus, and POMC-expressing neurons are critically involved in the control of appetite and energy balance (3). Mice and humans lacking all POMC-derived peptides are severely hyperphagic and obese (4). A role for genetic variation in or near the POMC locus in determination of obesity or obesity-related quantitative traits in the general population has been suggested by a number of independent studies (5,6). If the POMC gene itself is the causative gene, this would imply that relatively subtle variation in POMC structure or function is sufficient to significantly alter energy balance. This notion is supported by the association of a number of point mutations in POMC with obesity (7,8), although some of these appear to have the capacity for dominant-negative interference with wild-type melanocortins (9). Limited data on existing human POMC-null heterozygotes show a trend toward increased adiposity (10).In the present study, we report a patient homozygous for a novel frameshift mutation in POMC (C6906del) associated with severe obesity and ACTH deficiency. This mutation results in the complete loss of all POMC-derived peptides. A larg...

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Section: Discussionmentioning

confidence: 75%

Heterozygosity for a POMC-Null Mutation and Increased Obesity Risk in Humans

Farooqi

Drop

Clements³

et al. 2006

Diabetes

209

132

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“…The peak on 3q22-q24 was found at the SLC9A9 gene. The region 4q31-q34 overlaps with the region for which suggestive linkages were found in two previous linkage studies for physical fitness (FABP2 gene; Bouchard et al, 2000) and physical activity (UCP1 gene; Simonen et al, 2003). Future association studies should further clarify the possible role of these genes in athlete status.…”

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confidence: 72%

Genome-Wide Linkage Scan for Athlete Status in 700 British Female DZ Twin Pairs

Moor¹,

et al. 2007

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Association studies, comparing elite athletes with sedentary controls, have reported a number of genes that may be related to athlete status. The present study reports the first genome wide linkage scan for athlete status. Subjects were 4488 adult female twins from the TwinsUK Adult Twin Registry (793 monozygotic [MZ] and 1000 dizygotic [DZ] complete twin pairs, and single twins). Athlete status was measured by asking the twins whether they had ever competed in sports and what was the highest level obtained. Twins who had competed at the county or national level were considered elite athletes. Using structural equation modeling in Mx, the heritability of athlete status was estimated at 66%. Seven hundred DZ twin pairs that were successfully genotyped for 1946 markers (736 microsatellites and 1210 SNPs) were included in the linkage analysis. Identical-by-descent probabilities were estimated in Merlin for a 1 cM grid, taking into account the linkage disequilibrium of correlated SNPs. The linkage scan was carried out in Mx using the-approach. Suggestive linkages were found on chromosomes 3q22-q24 and 4q31-q34. Both areas converge with findings from previous studies using exercise phenotypes. The peak on 3q22-q24 was found at the SLC9A9 gene. The region 4q31-q34 overlaps with the region for which suggestive linkages were found in two previous linkage studies for physical fitness (FABP2 gene; Bouchard et al., 2000) and physical activity (UCP1 gene; Simonen et al., 2003). Future association studies should further clarify the possible role of these genes in athlete status.

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“…Thus, we can conclude that heredity, to some degree, contributes to the variation in Variability in habitual physical activity EE Wickel and JC Eisenmann PA levels between individuals; however, possibly more important, these results imply that proposed lifestyle strategies aimed at increasing levels of PA need to be different among people. Using the Bouchard activity diary, Simonen et al (2003a) provided additional evidence supporting the role of genetics to partially explain the variation in PA levels among individuals. Three PA phenotypes (inactivity, moderate to strenuous PA, and total daily activity level) derived from the Bouchard diary displayed encouraging linkage evidence for both PA (chromosome 2p22-p16) and IA (chromosomes 7p11.2, 20q13.1).…”

Section: Discussionmentioning

confidence: 99%

Within- and between-individual variability in estimated energy expenditure and habitual physical activity among young adults

Wickel

Eisenmann

2005

Eur J Clin Nutr

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Objective: To examine the within-and between-individual variability in the estimated total energy expenditure (TEE) and habitual physical activity (PA) in free-living young adults. We were specifically interested in the day-to-day variation. Design: Cross-sectional. Setting: University. Subjects: A total of 277 (125 males, 152 females) participants aged 18-24 years. Interventions: None. Main outcome measures: Subjects recorded their daily PA with the Bouchard 3-day diary. Descriptive statistics for TEE, moderate-to-vigorous physical activity (MVPA), inactivity (IA), and activity energy expenditure (AEE) were calculated and presented as a frequency distribution. Within-and between-individual variability were tested by RMANOVA and also presented as the coefficient of variation (CV). Results: Mean values for TEE, MVPA, AEE, and IA were comparable between males and females; however, considerable between-individual variability existed. Only MVPA showed a significant difference between sexes (Po0.05), due to slightly greater vigorous PA in males compared to females (8.0 and 6.8 kcal/kg/day, respectively; P ¼ 0.12). Results from the RMANOVA revealed no significant day-to-day variability in any TEE or PA variable and the CVs were not significantly different between males and females. TEE and IA displayed mean CVs of approximately 12% while mean CVs for AEE and MVPA approximated 32 and 84%, respectively. Conclusions: Results from this study suggest (1) a limited day-to-day variability in TEE and (2) a large degree of betweenindividual variation for TEE and PA exist. This study highlights the importance of understanding the variability associated with TEE, which is important for PA measurement and proper PA and nutritional recommendations. Sponsorship: None.

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Genome-Wide Linkage Scan for Physical Activity Levels in the Quebec Family Study

Abstract: This study identified several chromosomal regions harboring genes that may contribute to the propensity to be physically active or sedentary.

Cited by 72 publications

References 33 publications

Heterozygosity for a POMC-Null Mutation and Increased Obesity Risk in Humans

Heterozygosity for a POMC-Null Mutation and Increased Obesity Risk in Humans

Genome-Wide Linkage Scan for Athlete Status in 700 British Female DZ Twin Pairs

Within- and between-individual variability in estimated energy expenditure and habitual physical activity among young adults

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