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DOI: 10.1055/s-0038-1634098
Practical Considerations on the Use of Extreme Sib-pairs for Obesity
Publication History
Publication Date:
06 February 2018 (online)
Summary
Objectives: The extreme sib-pair approach has been shown to be a powerful strategy to identify susceptibility loci linked to quantitative traits. The body mass index is the usually assessed trait in genetic studies on human obesity. Environmental factors clearly play an important role for this trait. We hypothesized that the low weight of most sibs who were seemingly discordant to the obese index proband was influenced by other environmental and/or genetic factors like restrained eating or psychiatric disorders.
Methods: A screening questionnaire was sent to parents of all consecutively admitted patients three weeks prior to referral of index probands for inpatient treatment of obesity. The first 320 families were further investigated. Twenty-seven seemingly extremely discordant sib-pairs (ED) were identified and examined in detail.
Results: The low weight of most sibs who were seemingly discordant to the obese index proband was influenced by factors like restrained eating or psychiatric disorders. Only 20% of the interviewed ED could be considered as genuine ED.
Conclusion: We conclude that extensive medical evaluation is necessary if the aim is to guarantee genuine ED in family studies for human obesity. Non-paternity deserves specific attention in ED studies.
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References
- 1 Risch N, Zhang H. Extreme discordant sib pairs for mapping quantitative trait loci in humans. Science 1995; 268: 1584-9.
- 2 Boehnke M, Langefeld CD. Genetic association mapping based on discordant sib pairs: the discordant- alleles test. Am J Hum Genet 1998; 62: 950-61.
- 3 Horvath S, Laird NM. A discordant-sibship test for disequilibrium and linkage: no need for parental data. Am J Hum Genet 1998; 63: 1886-97.
- 4 Ziegler A, König IR. A Statistical Approach to Genetic Epidemiology: Concepts and Applications. Weinheim: Wiley-VCH 2006
- 5 Darvasi A, Soller M. Selective genotyping for determination of linkage between a marker locus and a quantitative trait. Theor Appl Genet 1992; 85: 353-9.
- 6 Mackinnon MJ, Georges MA. The effects of selection on linkage analysis for quantitative traits. Genetics 1992; 132: 1177-85.
- 7 Ziegler A, Hebebrand J. Sample size calculations for linkage analysis using extreme sib pairs based on segregation analysis with the quantitative phenotype body weight as an example. Genet Epidemiol 1998; 15: 577-93.
- 8 Allison DB. et al Extreme selection strategies in gene mapping studies of oligogenic quantitative traits do not always increase power. Hum Hered 1998; 48: 97-107.
- 9 Allison DB. The use of discordant sibling pairs for finding genetic loci linked to obesity: practical considerations. Int J Obes Relat Metab Disord 1996; 20: 553-60.
- 10 Neale MC, Neale BM, Sullivan PF. Nonpaternity in linkage studies of extremely discordant sib pairs. Am J Hum Genet 2002; 70: 526-9.
- 11 Ziegler A. Genetische Kartierung quantitativer Phänotypen. Eine Übersicht über modellfreie kopplungsanalytische Verfahren. München: Urban & Vogel, Medien und Medizinverlag 1999
- 12 Cerda-Flores RM. et al Estimation of nonpaternity in the Mexican population of Nuevo Leon: a validation study with blood group markers. Am J Phys Anthropol 1999; 109: 281-93.
- 13 Sykes B, Irven C. Surnames and the Y chromosome. Am J Hum Genet 2000; 66: 1417-9.
- 14 Magnusson PK, Rasmussen F. Familial resemblance of body mass index and familial risk of high and low body mass index. A study of young men in Sweden. Int J Obes Relat Metab Disord 2002; 26: 1225-31.
- 15 Himes JH, Dietz WH. Guidelines for overweight in adolescent preventive services: recommendations from an expert committee. The Expert Committee on Clinical Guidelines for Overweight in Adolescent Preventive Services. Am J Clin Nutr 1994; 59: 307-16.
- 16 Guo SS, Chumlea WC. Tracking of body mass index in children in relation to overweight in adulthood. Am J Clin Nutr 1999; 70
- 17 Allison DB. et al Assortative mating for relative weight: genetic implications. Behav Genet 1996; 26: 103-11.
- 18 WHO. Composite International Diagnostic Interview (CIDI). a) CIDI Interview Version 1.0, b) CIDI-User Manual, c) CIDI-Training-Manual, d) CIDI Computer Programs. Geneva: WHO 1990
- 19 APA. Diagnostic and Statistical Manual of Mental Disorders. Washington: American Psychiatric Association 1994
- 20 Stunkard AJ, Messick S. The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger. J Psychosom Res 1985; 29: 71-83.
- 21 Zhao H, Zhang H, Rotter JI. Cost-effective sibpair designs in the mapping of quantitative-trait loci. Am J Hum Genet 1997; 60: 1211-21.
- 22 Gu C, Rao DC. A linkage strategy for detection of human quantitative-trait loci. II. Optimization of study designs based on extreme sib pairs and generalized relative risk ratios. Am J Hum Genet 1997; 61: 211-22.
- 23 Devlin B. et al Linkage analysis of anorexia nervosa incorporating behavioral covariates. Hum Mol Genet 2002; 11: 689-96.
- 24 Elston RC. et al Mathematical assumptions versus biological reality: myths in affected sib pair linkage analysis. Am J Hum Genet 2005; 76: 152-6.
- 25 Zöllner S, Wen X, Hanchard NA, Herbert MA, Ober C, Pritchard JK. Evidence for extensive transmission distortion in the human genome. Am J Hum Genet 2004; 74: 62-72.
- 26 Pardo-Manuel de Villena F, Sapienza C. Nonrandom segregation during meiosis: the unfairness of females. Mamm Genome 2001; 12: 331-9.