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Distinguishing Population Stratification from Genuine Allelic Effects with Mx: Association of ADH2 with Alcohol Consumption
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Within-family genetic association estimates, such as those obtained from samples of siblings, can provide less biased estimates of direct genetic effects because they are unlikely to be affected by demographic and indirect genetic effects of parents.
“Within-family genetic association estimates, such as those obtained from samples of siblings, can provide less biased estimates of direct genetic effects because they are unlikely to be affected by demographic and indirect genetic effects of parents7,17,30–34.”
From Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects (2022) · cites this paper as [33]
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Posthuma, D., Beem, A. L., de Geus, E. J. C., van Baal, G. C. M., von Hjelmborg, J. B., Iachine, I., & Boomsma, D. I. (2003) · Twin Research · doi:10.1375/136905203770326367 · Cited by 416
“In association analysis the effects of measured alleles on a trait are tested, by incorporating fixed effects on the means using genetically related or unrelated subjects (Moxley et al., 2002; Neale et al., 1999; Neale, 2000; Zhu et al., 1999).”
MethodWithin-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects
Howe, L. J., Nivard, M. G., Morris, T. T., Hansen, A. F., Rasheed, H., Cho, Y., Chittoor, G., Ahlskog, R., Lind, P. A., Palviainen, T., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01062-7 · Cited by 377
Self-citationRecent advances in the genetic epidemiology and molecular genetics of substance use disorders
Kendler, K. S., Chen, X., Dick, D., Maes, H., Gillespie, N., Neale, M. C., & Riley, B. (2012) · Nature Neuroscience · doi:10.1038/nn.3018 · Cited by 179
Self-citationTwin–singleton differences in intelligence?
Posthuma, D., de Geus, E. D., Bleichrodt, N., & Boomsma, D. (2000) · Twin Research · doi:10.1375/twin.3.2.83 · Cited by 108
Dopamine transporter polymorphism associated with externalizing behavior problems in children
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Genetic linkage and association between chromosome 1q and working memory function in schizophrenia
Gasperoni, T. L., Ekelund, J., HUTTUNEN, M. O., Palmer, C. G. S., Tuulio‐Henriksson, A., Lönnqvist, J. K., Kaprio, J. A., Peltonen, L., & Cannon, T. D. (2002) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.10757 · Cited by 87
“…models twin variances and covariances in the usual manner except that the statement for the means includes two parameters for the effects of allelic differences: one for effects between-families and one for effects within-families [Fulker et al., 1999; Neale et al., 1999; Abecasis et al., 2000].”
BackgroundWithin-sibship GWAS improve estimates of direct genetic effectsPreprint
Howe, L. J., Nivard, M. G., Morris, T., Hansen, A. F., Rasheed, H., Cho, Y., Chittoor, G., Lind, P. A., Palviainen, T., van der Zee, M. D., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.05.433935 · Cited by 70
“Within-family genetic association estimates, such as those obtained from samples of siblings, can provide more accurate estimates of direct genetic effects because they are unaffected by demography and indirect genetic effects of parents [7, 17, 29-32].”
BackgroundSelf-citationBrumpton, B., Sanderson, E., Hartwig, F., Harrison, S., Vie, G. Å., Cho, Y., Howe, L., Hughes, A. M., Boomsma, D., Havdahl, A., et al. (2019) · bioRxiv · doi:10.1101/602516 · Cited by 75
Self-citationWall, T., Shea, S. H., Luczak, S. E., Cook, T. A. R., & Carr, L. (2005) · Journal of Abnormal Psychology · doi:10.1037/0021-843x.114.3.456 · Cited by 71
Hasin, D. S., Aharonovich, E., Liu, X., Mamman, Z., Matseoane, K., Carr, L. G., & Li, T. (2002) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2002.tb02673.x · Cited by 56
“Second, the ADH2 literature shows that ADH2 effects on alcohol dependence are consistent in many countries and population groups, including samples of twins (Heath et al., 2001; Neale et al., 1999).”
Hansell, N. K., Arpana Agrawal, A., Whitfield, J. B., Morley, K. I., Zhu, G., Lind, P. A., Pergadia, M. L., Madden, P. A. F., Todd, R. D., Heath, A. C., et al. (2008) · Twin Research and Human Genetics · doi:10.1375/twin.11.3.287 · Cited by 49
Self-citationβ-2 adrenergic receptor gene variations and blood pressure under stress in normal twins
Li, G.-H., Faulhaber, H., Rosenthal, M., Schuster, H., Jordan, J., Timmermann, B., Hoehe, M., Luft, F. C., & Busjahn, A. (2001) · doi:10.1111/1469-8986.3830485 · Cited by 44
Reynolds, C. A., Prince, J. A., Feuk, L., Brookes, A. J., Gatz, M., & Pedersen, N. L. (2006) · Behavior Genetics · doi:10.1007/s10519-005-9027-6 · Cited by 36
Combined Linkage and Association Tests in Mx
Posthuma, D., de Geus, E. D., Boomsma, D., & Neale, M. (2004) · Behavior Genetics · doi:10.1023/b:bege.0000013732.19486.74 · Cited by 32
“Combining linkage analysis and association analysis has already proved to be a powerful tool in gene finding (e.g., Neale et al., 1999; Trembath et al., 1997; Zhu et al., 1999; see Beekman et al., 2003 for a practical implementation of the method described in the present paper).”
MethodInfluentialSelf-citationIliadou, A., Lichtenstein, P., Morgenstern, R., Forsberg, L., Svensson, R., de Faire, U., Martin, N., & Pedersen, N. (2002) · Journal of Hypertension · doi:10.1097/00004872-200208000-00017 · Cited by 30
Self-citationBirley, A. J., Whitfield, J. B., Neale, M. C., Duffy, D. L., Heath, A. C., Boomsma, D. I., & Martin, N. G. (2005) · Behavior Genetics · doi:10.1007/s10519-005-3851-6 · Cited by 26
“…sizes and statistical significance for tests of association involving the ADH1B and ADH1C loci, any such further partition would be uninformative A stronger association of ADH1C locus with alcohol consumption in the same ACTS subjects was not due to population stratification (Neale et al., 1999).”
BackgroundSelf-citationvan der Sluis, S., Dolan, C. V., Neale, M. C., & Posthuma, D. (2008) · Behavior Genetics · doi:10.1007/s10519-008-9201-8 · Cited by 23
“This design was extended by Neale et al. (1999) to include covariates, and by Abecasis et al. (2000a) to include multiple sibs, and parental information.”
BackgroundResultSelf-citationYoung, S., Smolen, A., Stallings, M., Corley, R., & Hewitt, J. (2003) · Journal of Child Psychology and Psychiatry and Allied Disciplines · doi:10.1111/1469-7610.00180 · Cited by 18
Joint Tests of Linkage and Association for Quantitative Traits
Allison, D. B., & Neale, M. C. (2001) · Theoretical Population Biology · doi:10.1006/tpbi.2001.1544 · Cited by 16
“Fulker and Cherny (1998) (see also Neale et al., 1999; Neale, 2001) showed how the stratification can be removed by fitting models that specify separate mean components between families and within families.”
BackgroundMethodSelf-citationWessel, J., Schork, A. J., Tiwari, H. K., & Schork, N. J. (2007) · Genetic Epidemiology · doi:10.1002/gepi.20241 · Cited by 12
“However, there is very little in the literature on the use of genotypically discordant twins and siblings for association studies, although some studies have shown that twins can be useful for controlling for genetic background effects and stratification that may obscure or confound association studies [Whitfield et a…”
The use of Mx for association and linkage analysis
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Self-citationGillespie, N., & Neale, M. (2006) · Twin Research and Human Genetics · doi:10.1375/183242706777591380 · Cited by 11
“Under the QTL model, the class membership probabilities for the DZ pairs were calculated according a simple diallelic dominant locus (e.g., Neale et al., 1999, see Table 1).”
BackgroundMethodSelf-citationWiart, A., Jepson, A., Banya, W., Bennett, S., Whittle, H., Martin, N., & Hill, A. (2004) · Twin Research · doi:10.1375/twin.7.6.578 · Cited by 9
“Mean differences in phenotype as a function of allelic effect could occur from either functional effects of the locus itself, or from linkage disequilibrium with a nearby functional site, or association could be spurious arising from population stratification (Neale et al., 1999).”
Self-citationPower of QTL detection using association tests with family controls
Hernández-Sánchez, J., Haley, C., & Visscher, P. (2003) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201042 · Cited by 9
Notes on Three Decades of Methodology Workshops
MAES, H. H. M. (2021) · Behavior Genetics · doi:10.1007/s10519-021-10049-9 · Cited by 4
Iliadou, A., Lichtenstein, P., Ahlberg, S., Hoffstedt, J., Arner, P., Schalling, M., Pedersen, N., & Lavebratt, C. (2003) · Twin research : the official journal of the International Society for Twin Studies · doi:10.1375/136905203321536290 · Cited by 3
“For the models fitted, the degrees of freedom and twice the log-likelihood probability were computed by means of the structural equation-modeling package MX (Neale et al., 1999).”
MethodReview: Genetic epidemiological approaches in the study of risk factors for cardiovascular disease
Iliadou, A., & Snieder, H. (2003) · European Journal of Epidemiology · doi:10.1023/b:ejep.0000020399.19615.6c · Cited by 3
“In recent years, powerful statistical models were presented that jointly perform tests of both linkage and association controlling for spurious associations due to population stratification and admixture [56, 57].”
BackgroundIliadou, A., Lichtenstein, P., Ahlberg, S., Hoffstedt, J., Arner, P., Schalling, M., Pedersen, N., & Lavebratt, C. (2003) · Twin Research · doi:10.1375/twin.6.2.162
“For the models fitted, the degrees of freedom and twice the log-likelihood probability were computed by means of the structural equation-modeling package MX (Neale et al., 1999).”
MethodNeale (2000) · doi:10.1002/(sici)1098-2272(200004)18:4
Self-citation
Metadata
- Authors
- Neale, M. C., Cherny, S. S., Sham, P. C., Whitfield, J. B., Heath, A. C., Birley, A. J., & Martin, N. G.
- Affiliations
- Virginia Commonwealth University (US)
- University of Colorado Boulder (US)
- Royal Prince Alfred Hospital (AU)
- Washington University in St. Louis (US)
- QIMR Berghofer Medical Research Institute (AU)
- Venue
- Behavior Genetics
- Published
- 1999-07
- Volume
- 29
- Issue
- 4
- Pages
- 233-243
- ISSN
- 0001-8244 (ISSN-L)
- 1573-3297
- OpenAlex
- W2163479103
- Cited by
- 29
- References
- 36
- Citations by year
- 2022: 2 · 2021: 2 · 2020: 1 · 2012: 1
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Behavior Genetics (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Keywords
- population stratification, linkage disequilibrium, ADH2, alcohol consumption, alcohol dehydrogenase, genetic association, twin pairs, genetic architecture, admixture
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