Positive results in association studies are associated with departure from Hardy-Weinberg equilibrium: hint for genotyping error?

Hundreds of genome-wide association studies were conducted to map the disease genes on autosomes in human beings. It is known that many complex diseases are sex-determined and X chromosome is expected to play an important role. However, only a few single-nucleotide polymorphisms on X chromosome were found to be significantly associated with the diseases under study. On the other hand, to balance the genetic effect between two sexes, X chromosome inactivation occurs in most of X-linked genes by silencing one copy of two X chromosomes in females and dosage compensation is achieved. A few association studies on X chromosome incorporated the information on dosage compensation. However, some of them require the assumption of Hardy–Weinberg equilibrium and some need to specify the underlying genetic model. Therefore, in this article, we propose a novel method for association by taking account of different dosage compensation patterns. The proposed test is a robust approach because it requires neither specifying the underlying genetic models nor the assumption of Hardy–Weinberg equilibrium. Further, the proposed method allows for different deviations from Hardy–Weinberg equilibrium between cases and controls. Simulation results demonstrate that our proposed method generally outperforms the existing methods in terms of controlling the size and the test power. Finally, we apply the proposed test to the meta-analysis of the Graves' disease data for its practical use.

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Polymorphisms in MyoD1, MyoG, MyF5, MyF6, and MSTN genes in Santa Inês sheep

Pesquisa Agropecuária Brasileira ◽

10.1590/s1678-3921.pab2019.v54.01132 ◽

2019 ◽

Vol 54 ◽

Cited By ~ 1

Author(s):

Luis Paulo Batista Sousa Junior ◽

Ariana Nascimento Meira ◽

Hymerson Costa Azevedo ◽

Evandro Nevez Muniz ◽

Luiz Lehmann Coutinho ◽

...

Keyword(s):

Association Studies ◽

Ovis Aries ◽

Allele Frequencies ◽

Reference Sequence ◽

Coding Region ◽

Weinberg Equilibrium ◽

Hardy Weinberg Equilibrium ◽

Santa Inês ◽

Genotype And Allele Frequencies

Abstract: The objective of this work was to sequence the MyoD1, MyoG, MyF5, MyF6, and MSTN genes and to identify polymorphisms in Santa Inês sheep (Ovis aries). A total of 192 lambs with 240 days of age were evaluated, and these genes were sequenced to be compared with the reference sequence in the Ovis aries genome. Genotype and allele frequencies were estimated, and the Hardy-Weinberg equilibrium was tested. Fragments containing 2,493 bp (MyoD1), 1,836 bp (MyoG), 2,813 bp (MyF5), 1,126 bp (MyF6), and 2,380 bp (MSTN) were obtained, and, in these sequences, 160 variants were identified. These polymorphisms were distributed as follows: 59 (MyoD1), 24 (MyoG), 63 (MyF5), 4 (MyF6), and 10 (MSTN). One hundred and four were novel polymorphisms, 45 in MyoD1, 2 in MyoG, 56 in MyF5, and 1 in MSTN. Regarding site, 61 were in intron (27 in MyoD1, 16 in MyoG, 5 in MyF5, 3 in MyF6, and 10 in MSTN), 87 in coding region (22 in MyoD1, 8 in MyoG, 56 in MyF5, and 1 in MyF6), and 12 on 3’UTR (10 in MyoD1 and 2 in MyF5). Therefore, the MyoD family and MSTN genes have several polymorphisms in Santa Inês sheep, which can be useful for association studies.

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